rs16872235

chr5-74741561-T-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032380.5(GFM2):c.898A>T(p.Ser300Cys) variant causes a missense change. The variant allele was found at a frequency of 0.12 in 1,580,296 control chromosomes in the GnomAD database, including 12,408 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.13 (1483 hom., cov: 32)
  • Exomes 𝑓: 0.12 (10925 hom.)
• Consequence: GFM2 NM_032380.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.88

Genes affected

GFM2 (HGNC:29682): (GTP dependent ribosome recycling factor mitochondrial 2) Eukaryotes contain two protein translational systems, one in the cytoplasm and one in the mitochondria. Mitochondrial translation is crucial for maintaining mitochondrial function and mutations in this system lead to a breakdown in the respiratory chain-oxidative phosphorylation system and to impaired maintenance of mitochondrial DNA. This gene encodes one of the mitochondrial translation elongation factors, which is a GTPase that plays a role at the termination of mitochondrial translation by mediating the disassembly of ribosomes from messenger RNA . Its role in the regulation of normal mitochondrial function and in disease states attributed to mitochondrial dysfunction is not known. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016189218).
• BP6: Variant 5-74741561-T-A is Benign according to our data. Variant chr5-74741561-T-A is described in ClinVar as [Benign]. Clinvar id is 137472.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GFM2	NM_032380.5	c.898A>T	p.Ser300Cys	missense_variant	11/21	ENST00000296805.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GFM2	ENST00000296805.8	c.898A>T	p.Ser300Cys	missense_variant	11/21	1	NM_032380.5	P1

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20394 AN: 152014 Hom.: 1483 Cov.: 32

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.0215

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.151

GnomAD3 exomes AF: 0.112 AC: 26851 AN: 239636 Hom.: 1766 AF XY: 0.114 AC XY: 14793 AN XY: 129598

Gnomad AFR exome AF: 0.178

Gnomad AMR exome AF: 0.0838

Gnomad ASJ exome AF: 0.165

Gnomad EAS exome AF: 0.0228

Gnomad SAS exome AF: 0.102

Gnomad FIN exome AF: 0.112

Gnomad NFE exome AF: 0.123

Gnomad OTH exome AF: 0.131

GnomAD4 exome AF: 0.119 AC: 169999 AN: 1428164 Hom.: 10925 Cov.: 25 AF XY: 0.119 AC XY: 84879 AN XY: 711576

Gnomad4 AFR exome AF: 0.187

Gnomad4 AMR exome AF: 0.0885

Gnomad4 ASJ exome AF: 0.162

Gnomad4 EAS exome AF: 0.0154

Gnomad4 SAS exome AF: 0.105

Gnomad4 FIN exome AF: 0.115

Gnomad4 NFE exome AF: 0.121

Gnomad4 OTH exome AF: 0.126

GnomAD4 genome AF: 0.134 AC: 20399 AN: 152132 Hom.: 1483 Cov.: 32 AF XY: 0.133 AC XY: 9914 AN XY: 74372

Gnomad4 AFR AF: 0.182

Gnomad4 AMR AF: 0.116

Gnomad4 ASJ AF: 0.153

Gnomad4 EAS AF: 0.0216

Gnomad4 SAS AF: 0.102

Gnomad4 FIN AF: 0.106

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.148

Alfa AF: 0.127 Hom.: 1014

Bravo AF: 0.139

TwinsUK AF: 0.133 AC: 492

ALSPAC AF: 0.124 AC: 477

ESP6500AA AF: 0.182 AC: 798

ESP6500EA AF: 0.123 AC: 1051

ExAC AF: 0.114 AC: 13770

Asia WGS AF: 0.0720 AC: 248 AN: 3468

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 17, 2013

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. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.25
Cadd	Uncertain	25
Dann	Uncertain	0.98
DEOGEN2	Benign	0.013	T;.;T;.;T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.97	D
MetaRNN	Benign	0.0016	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L;L;L;L;.
MutationTaster	Benign	0.000015	P;P;P;P
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-2.2	N;N;N;N;N
REVEL	Benign	0.17
Sift	Uncertain	0.0060	D;D;D;D;T
Sift4G	Uncertain	0.025	D;D;D;D;.
Polyphen		0.99	D;D;D;D;.
Vest4		0.12
MPC		0.64
ClinPred		0.022	T
GERP RS		5.9
Varity_R		0.36
gMVP		0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs16872235; hg19: chr5-74037386;