VCV000462898.47 - ClinVar

NM_000481.4(AMT):c.631G>A (p.Glu211Lys)

Germline

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.

(10)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Benign/Likely benign

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000481.4(AMT):c.631G>A (p.Glu211Lys)

Variation ID: 462898 Accession: VCV000462898.47

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 3p21.31 3: 49419325 (GRCh38) [ NCBI UCSC ] 3: 49456758 (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	Dec 26, 2017	Dec 22, 2024	Oct 1, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_000481.4:c.631G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000472.2:p.Glu211Lys	missense
NM_001164710.2:c.499G>A	NP_001158182.1:p.Glu167Lys	missense
NM_001164711.2:c.463G>A	NP_001158183.1:p.Glu155Lys	missense
NM_001164712.2:c.631G>A	NP_001158184.1:p.Glu211Lys	missense
NR_028435.2:n.640G>A		non-coding transcript variant
NC_000003.12:g.49419325C>T
NC_000003.11:g.49456758C>T
NG_015986.1:g.8354G>A
LRG_537:g.8354G>A
LRG_537t1:c.631G>A	LRG_537p1:p.Glu211Lys

... more HGVS ... less HGVS

Protein change

E211K, E155K, E167K

Other names

Canonical SPDI

NC_000003.12:49419324:C:T

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

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.

0.00719 (T)

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

Exome Aggregation Consortium (ExAC) 0.01103

1000 Genomes Project 30x 0.00625

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00654

1000 Genomes Project 0.00719

Trans-Omics for Precision Medicine (TOPMed) 0.00720

The Genome Aggregation Database (gnomAD) 0.00735

Links

ClinGen: CA2398296 dbSNP: rs116192290 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.
AMT		-	-	GRCh38 GRCh37	629	721

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.
Glycine encephalopathy	Benign/Likely benign (7)	criteria provided, multiple submitters, no conflicts	Feb 1, 2024	RCV000549987.18
not provided	Benign (2)	criteria provided, multiple submitters, no conflicts	Oct 1, 2024	RCV000991518.27
not specified	Benign (1)	no assertion criteria provided	-	RCV001573069.1

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.	More information 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.
Likely benign (Oct 09, 2014)	criteria provided, single submitter (ACGS Guidelines, 2013) Method: clinical testing	Glycine encephalopathy 1 Affected status: yes Allele origin: germline	Genome Diagnostics Laboratory, University Medical Center Utrecht Study: VKGL Data-share Consensus Accession: SCV000743157.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018
Benign (Feb 01, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Glycine encephalopathy Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000636427.5 First in ClinVar: Dec 26, 2017 Last updated: Feb 20, 2024
Likely benign (May 28, 2019)	criteria provided, single submitter (Mendelics Assertion Criteria 2017) Method: clinical testing	Glycine encephalopathy 1 Affected status: unknown Allele origin: unknown	Mendelics Accession: SCV001136523.1 First in ClinVar: Jan 10, 2020 Last updated: Jan 10, 2020
Benign (Sep 11, 2018)	criteria provided, single submitter (Athena Diagnostics Criteria) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Athena Diagnostics Accession: SCV001143008.1 First in ClinVar: Jan 19, 2020 Last updated: Jan 19, 2020	Publications: PubMed (5) PubMed: 10873393‚ 27884173‚ 27620832‚ 12948742‚ 22171071
Likely benign (Apr 27, 2017)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Glycine encephalopathy 1 Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV001311639.1 First in ClinVar: May 31, 2020 Last updated: May 31, 2020	Comment: This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more) This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
Likely benign (Jul 10, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Glycine encephalopathy 1 Affected status: no Allele origin: germline	Genome-Nilou Lab Accession: SCV001762853.1 First in ClinVar: Aug 05, 2021 Last updated: Aug 05, 2021	Sex: mixed
Benign (Oct 01, 2024)	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2) Method: clinical testing	not provided Affected status: yes Allele origin: germline	CeGaT Center for Human Genetics Tuebingen Accession: SCV001153957.28 First in ClinVar: Feb 03, 2020 Last updated: Dec 22, 2024	Comment: AMT: BS1, BS2 Number of individuals with the variant: 46
Benign (-)	no assertion criteria provided Method: clinical testing	Glycine encephalopathy 1 Affected status: yes Allele origin: germline	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV000734285.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018
Benign (Sep 16, 2020)	no assertion criteria provided Method: clinical testing	Non-ketotic hyperglycinemia Affected status: unknown Allele origin: germline	Natera, Inc. Accession: SCV001456314.1 First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) Study: VKGL Data-share Consensus Accession: SCV001798398.1 First in ClinVar: Aug 21, 2021 Last updated: Aug 21, 2021

Comment:

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Revisiting the morbid genome of Mendelian disorders.	Abouelhoda M	Genome biology	2016	PMID: 27884173
Genetic association of the glycine cleavage system genes and myelomeningocele.	Shah RH	Birth defects research. Part A, Clinical and molecular teratology	2016	PMID: 27620832
Mutations in genes encoding the glycine cleavage system predispose to neural tube defects in mice and humans.	Narisawa A	Human molecular genetics	2012	PMID: 22171071
Molecular genetic and potential biochemical characteristics of patients with T-protein deficiency as a cause of glycine encephalopathy (NKH).	Toone JR	Molecular genetics and metabolism	2003	PMID: 12948742
Biochemical and molecular investigations of patients with nonketotic hyperglycinemia.	Toone JR	Molecular genetics and metabolism	2000	PMID: 10873393

Text-mined citations for rs116192290 ...

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 Jan 13, 2025

ClinVar Genomic variation as it relates to human health

NM_000481.4(AMT):c.631G>A (p.Glu211Lys)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs116192290 ...