NM_024996.7(GFM1):c.521A>G (p.Asn174Ser) AND not provided

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Apr 16, 2023
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:: RCV000657878.6

Allele description [Variation Report for NM_024996.7(GFM1):c.521A>G (p.Asn174Ser)]

NM_024996.7(GFM1):c.521A>G (p.Asn174Ser)

Gene:

GFM1:G elongation factor mitochondrial 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3q25.32

Genomic location:

Preferred name:

NM_024996.7(GFM1):c.521A>G (p.Asn174Ser)

HGVS:

NC_000003.12:g.158646896A>G
NG_008441.1:g.7369A>G
NM_001308164.2:c.521A>G
NM_001308166.2:c.521A>G
NM_001374355.1:c.521A>G
NM_001374356.1:c.521A>G
NM_001374357.1:c.296A>G
NM_001374358.1:c.234+1115A>G
NM_001374359.1:c.5+1115A>G
NM_001374360.1:c.5+1115A>G
NM_001374361.1:c.5+1115A>G
NM_024996.7:c.521A>GMANE SELECT
NP_001295093.1:p.Asn174Ser
NP_001295095.1:p.Asn174Ser
NP_001361284.1:p.Asn174Ser
NP_001361285.1:p.Asn174Ser
NP_001361286.1:p.Asn99Ser
NP_079272.4:p.Asn174Ser
NP_079272.4:p.Asn174Ser
NC_000003.11:g.158364685A>G
NM_024996.5:c.521A>G
NR_164499.1:n.629A>G
NR_164500.1:n.629A>G
NR_164502.1:n.629A>G
Q96RP9:p.Asn174Ser

Protein change:

N174S; ASN174SER

Links:

UniProtKB: Q96RP9#VAR_021512; OMIM: 606639.0001; dbSNP: rs119470018

NCBI 1000 Genomes Browser:

rs119470018

Molecular consequence:

NM_001374358.1:c.234+1115A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001374359.1:c.5+1115A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001374360.1:c.5+1115A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001374361.1:c.5+1115A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001308164.2:c.521A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001308166.2:c.521A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001374355.1:c.521A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001374356.1:c.521A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001374357.1:c.296A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_024996.7:c.521A>G - missense variant - [Sequence Ontology: SO:0001583]
NR_164499.1:n.629A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_164500.1:n.629A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_164502.1:n.629A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000779640	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely pathogenic (May 29, 2019)	germline	clinical testing	Citation Link,
SCV003525469	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Apr 16, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 21364917, 15537906, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000779640

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Likely pathogenic
(May 29, 2019)

germline

clinical testing

Citation Link,

SCV003525469

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Apr 16, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

The Drosophila mitochondrial translation elongation factor G1 contains a nuclear localization signal and inhibits growth and DPP signaling.

Trivigno C, Haerry TE.

PLoS One. 2011 Feb 25;6(2):e16799. doi: 10.1371/journal.pone.0016799.

PubMed [citation]

PMID:: 21364917
PMCID:: PMC3045377

Mutant mitochondrial elongation factor G1 and combined oxidative phosphorylation deficiency.

Coenen MJ, Antonicka H, Ugalde C, Sasarman F, Rossi R, Heister JG, Newbold RF, Trijbels FJ, van den Heuvel LP, Shoubridge EA, Smeitink JA.

N Engl J Med. 2004 Nov 11;351(20):2080-6.

PubMed [citation]

PMID:: 15537906

See all PubMed Citations (3)

Details of each submission

From GeneDx, SCV000779640.4

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

Description

Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 15537906, 26937387, 21364917, 21986555)

#	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 Labcorp Genetics (formerly Invitae), Labcorp, SCV003525469.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on GFM1 function (PMID: 21364917). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt GFM1 protein function. ClinVar contains an entry for this variant (Variation ID: 4160). This missense change has been observed in individual(s) with combined oxidative phosphorylation deficiency (PMID: 15537906). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs119470018, gnomAD 0.004%). This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 174 of the GFM1 protein (p.Asn174Ser).

#	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

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine