VCV000203840.50 - ClinVar

NM_002454.3(MTRR):c.1653G>A (p.Pro551=)

Germline

Classification

criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.

Benign
Benign (7)

7 out of 8 submissions contributed to this classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_002454.3(MTRR):c.1653G>A (p.Pro551=)

Variation ID: 203840 Accession: VCV000203840.50

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 5p15.31 5: 7895829 (GRCh38) [ NCBI UCSC ] 5: 7895942 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Jul 18, 2015	Jul 27, 2026	Jun 1, 2026

HGVS

Nucleotide	Protein	Molecular consequence
NM_002454.3:c.1653G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_002445.2:p.Pro551=	synonymous
NM_001364440.2:c.1653G>A	NP_001351369.1:p.Pro551=	synonymous
NM_001364441.2:c.1653G>A	NP_001351370.1:p.Pro551=	synonymous
NM_001364442.2:c.1653G>A	NP_001351371.1:p.Pro551=	synonymous
NM_024010.4:c.1653G>A	NP_076915.3:p.Pro551=	synonymous
NR_134480.2:n.1732G>A		non-coding transcript variant
NR_134481.2:n.1657G>A		non-coding transcript variant
NR_134482.2:n.1592G>A		non-coding transcript variant
NR_157168.2:n.1706G>A		non-coding transcript variant
NR_157169.2:n.1566G>A		non-coding transcript variant
NR_157170.2:n.1732G>A		non-coding transcript variant
NR_157171.2:n.1589G>A		non-coding transcript variant
NR_157172.2:n.1503G>A		non-coding transcript variant
NR_157173.2:n.1743G>A		non-coding transcript variant
NR_157174.2:n.1744G>A		non-coding transcript variant
NR_157175.2:n.1898G>A		non-coding transcript variant
NR_157176.2:n.2061G>A		non-coding transcript variant
NR_157177.2:n.1741G>A		non-coding transcript variant
NR_157178.2:n.1769G>A		non-coding transcript variant
NC_000005.10:g.7895829G>A
NC_000005.9:g.7895942G>A
NG_008856.1:g.31726G>A

... more HGVS ... less HGVS

Protein change

Other names

p.P578P:CCG>CCA
p.Pro551=

Canonical SPDI

NC_000005.10:7895828:G:A

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

0.00359 (A)

Allele frequency Help The frequency of the allele represented by this VCV record.

The Genome Aggregation Database (gnomAD) 0.00699

1000 Genomes Project 30x 0.00328

1000 Genomes Project 0.00359

The Genome Aggregation Database (gnomAD), exomes 0.00803

Trans-Omics for Precision Medicine (TOPMed) 0.00609

The Genome Aggregation Database (gnomAD) 0.00700

Exome Aggregation Consortium (ExAC) 0.00887

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00761

The Genome Aggregation Database (gnomAD), exomes 0.01020

Links

ClinGen: CA312751 dbSNP: rs139206262 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
MTRR		Gene associated with autosomal recessive phenotype	No evidence available	GRCh38 GRCh37	1080	1303

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
not specified	Benign (2)	criteria provided, multiple submitters, no conflicts	Jul 23, 2025	RCV000186040.10
Disorders of Intracellular Cobalamin Metabolism	Benign (1)	criteria provided, single submitter	Jan 13, 2018	RCV000347256.13
Methylcobalamin deficiency type cblE	Benign (2)	criteria provided, single submitter	Feb 4, 2026	RCV000551951.22
not provided	Benign (3)	criteria provided, multiple submitters, no conflicts	Jun 1, 2026	RCV001812181.41

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	Expand all rows Collapse all rows Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Benign (Aug 11, 2014) C Contributing to aggregate classification	criteria provided, single submitter (GeneDx Variant Classification (06012015))	not specified	GeneDx Accession: SCV000239004.10 First in ClinVar: Jul 18, 2015 Last updated: Jul 18, 2015	Comment: show This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Benign (-) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	not provided (Autosomal recessive inheritance)	Breakthrough Genomics, Breakthrough Genomics Accession: SCV005298622.1 First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024	Observation: 1 Collection method: not provided Allele origin: germline Affected status: yes Observation 1 Collection method: not provided Allele origin: germline Affected status: yes

Benign (Sep 03, 2024) C Contributing to aggregate classification	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2024)	not provided	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories Accession: SCV001473044.5 First in ClinVar: Jan 26, 2021 Last updated: Mar 11, 2025	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Benign (Jul 23, 2025) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Not specified	Mayo Clinic Laboratories, Mayo Clinic Accession: SCV007320676.1 First in ClinVar: Jan 17, 2026 Last updated: Jan 17, 2026	Comment: show BA1, BP4, BP7 (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Number of individuals with the variant: 1

Benign (Feb 04, 2026) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Methylcobalamin deficiency type cblE	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000641848.10 First in ClinVar: Dec 26, 2017 Last updated: Feb 15, 2026	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Benign (Jan 13, 2018) C Contributing to aggregate classification	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Disorders of Intracellular Cobalamin Metabolism	Illumina Laboratory Services, Illumina Accession: SCV000458450.3 First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020	Comment: show This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Benign (Jun 01, 2026) C Contributing to aggregate classification	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	not provided	CeGaT Center for Human Genetics Tuebingen Accession: SCV004153917.23 First in ClinVar: Nov 20, 2023 Last updated: Jul 27, 2026	Comment: show MTRR: BP4, BP7, BS1, BS2 (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes Number of individuals with the variant: 14

Benign (Sep 16, 2020) N Not contributing to aggregate classification	no assertion criteria provided	CblE complementation type homocystinuria-megaloblastic anemia due to defect in cobalamin metabolism	Natera, Inc. Accession: SCV001458154.1 First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Comment:

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

Comment:

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

Citations for germline classification of this variant

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for rs139206262 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Jul 27, 2026