NM_023936.2(MRPS34):c.94C>T (p.Gln32Ter) AND not provided

Germline classification:: Pathogenic/Likely pathogenic (4 submissions)
Last evaluated:: Jan 22, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000760555.32

Allele description [Variation Report for NM_023936.2(MRPS34):c.94C>T (p.Gln32Ter)]

NM_023936.2(MRPS34):c.94C>T (p.Gln32Ter)

Genes:

EME2:essential meiotic structure-specific endonuclease subunit 2 [Gene - OMIM - HGNC]
MRPS34:mitochondrial ribosomal protein S34 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16p13.3

Genomic location:

Preferred name:

NM_023936.2(MRPS34):c.94C>T (p.Gln32Ter)

Other names:

MRPS34, GLN32TER (rs763672163); NM_001300900.1:c.94C>T(p.Gln32Ter); NM_023936.1:c.94C>T(p.Gln32Ter)

HGVS:

NC_000016.10:g.1773026G>A
NM_001300900.2:c.94C>T
NM_023936.2:c.94C>TMANE SELECT
NP_001287829.1:p.Gln32Ter
NP_076425.1:p.Gln32Ter
NC_000016.9:g.1823027G>A
NC_000016.9:g.1823027G>A
NM_001300900.1:c.94C>T
NM_023936.1:c.94C>T

Protein change:

Q32*; GLN32TER

Links:

OMIM: 611994.0004; dbSNP: rs763672163

NCBI 1000 Genomes Browser:

rs763672163

Molecular consequence:

NM_001300900.2:c.94C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_023936.2:c.94C>T - nonsense - [Sequence Ontology: SO:0001587]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000890446	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Sep 16, 2023)	germline	clinical testing	Citation Link,
SCV001149646	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Likely pathogenic (Nov 1, 2023)	germline	clinical testing	Citation Link,
SCV001208611	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 22, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 28777931, 28492532
SCV005199168	Clinical Genetics Laboratory, Skane University Hospital Lund	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 27, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Biallelic Mutations in MRPS34 Lead to Instability of the Small Mitoribosomal Subunit and Leigh Syndrome.

Lake NJ, Webb BD, Stroud DA, Richman TR, Ruzzenente B, Compton AG, Mountford HS, Pulman J, Zangarelli C, Rio M, Boddaert N, Assouline Z, Sherpa MD, Schadt EE, Houten SM, Byrnes J, McCormick EM, Zolkipli-Cunningham Z, Haude K, Zhang Z, Retterer K, Bai R, et al.

Am J Hum Genet. 2017 Aug 3;101(2):239-254. doi: 10.1016/j.ajhg.2017.07.005. Erratum in: Am J Hum Genet. 2018 Apr 5;102(4):713. doi: 10.1016/j.ajhg.2018.03.015.

PubMed [citation]

PMID:: 28777931
PMCID:: PMC5544391

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

See all PubMed Citations (3)

Details of each submission

From GeneDx, SCV000890446.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 28777931, 30358850, 30566640, 35326425, 37385809)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From CeGaT Center for Human Genetics Tuebingen, SCV001149646.26

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001208611.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change creates a premature translational stop signal (p.Gln32*) in the MRPS34 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MRPS34 are known to be pathogenic (PMID: 28777931). This variant is present in population databases (rs763672163, gnomAD 0.1%). This premature translational stop signal has been observed in individuals with Leigh syndrome, transient metabolic acidosis and hemodynamic instability related to tubulopathy (PMID: 28777931). ClinVar contains an entry for this variant (Variation ID: 438635). For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Clinical Genetics Laboratory, Skane University Hospital Lund, SCV005199168.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 8, 2024

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