3-158644652-T-C

Position:

chr3-158644652-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_024996.7(GFM1):c.18T>C(p.Ala6=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.538 in 1,572,136 control chromosomes in the GnomAD database, including 230,856 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.58 ( 26251 hom., cov: 33)

Exomes 𝑓: 0.53 ( 204605 hom. )

Consequence

GFM1
NM_024996.7 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.527

Variant links:

Genes affected

GFM1 (HGNC:13780): (G elongation factor mitochondrial 1) 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. Its role in the regulation of normal mitochondrial function and in different disease states attributed to mitochondrial dysfunction is not known. [provided by RefSeq, Jul 2008]

GFM1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 3-158644652-T-C is Benign according to our data. Variant chr3-158644652-T-C is described in ClinVar as [Benign]. Clinvar id is 343919.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-158644652-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.527 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.719 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GFM1	NM_024996.7 linkuse as main transcript	c.18T>C	p.Ala6=	synonymous_variant	1/18	ENST00000486715.6	NP_079272.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GFM1	ENST00000486715.6 linkuse as main transcript	c.18T>C	p.Ala6=	synonymous_variant	1/18	1	NM_024996.7	ENSP00000419038	P1	Q96RP9-1
GFM1	ENST00000264263.9 linkuse as main transcript	c.18T>C	p.Ala6=	synonymous_variant	1/19	5		ENSP00000264263		Q96RP9-2
GFM1	ENST00000478576.5 linkuse as main transcript	c.18T>C	p.Ala6=	synonymous_variant	1/14	2		ENSP00000418755
GFM1	ENST00000478254.5 linkuse as main transcript	c.18T>C	p.Ala6=	synonymous_variant, NMD_transcript_variant	1/18	5		ENSP00000417225

Frequencies

GnomAD3 genomes

AF:

0.578

AC:

87839

AN:

152012

Hom.:

26201

Cov.:

show subpopulations

Gnomad AFR

AF:

0.725

Gnomad AMI

AF:

0.480

Gnomad AMR

AF:

0.539

Gnomad ASJ

AF:

0.507

Gnomad EAS

AF:

0.340

Gnomad SAS

AF:

0.599

Gnomad FIN

AF:

0.529

Gnomad MID

AF:

0.599

Gnomad NFE

AF:

0.526

Gnomad OTH

AF:

0.556

GnomAD3 exomes

AF:

0.543

AC:

98331

AN:

181152

Hom.:

27215

AF XY:

0.545

AC XY:

53213

AN XY:

97550

show subpopulations

Gnomad AFR exome

AF:

0.731

Gnomad AMR exome

AF:

0.566

Gnomad ASJ exome

AF:

0.523

Gnomad EAS exome

AF:

0.327

Gnomad SAS exome

AF:

0.604

Gnomad FIN exome

AF:

0.516

Gnomad NFE exome

AF:

0.538

Gnomad OTH exome

AF:

0.527

GnomAD4 exome

AF:

0.534

AC:

758217

AN:

1420006

Hom.:

204605

Cov.:

AF XY:

0.536

AC XY:

376182

AN XY:

702286

show subpopulations

Gnomad4 AFR exome

AF:

0.736

Gnomad4 AMR exome

AF:

0.562

Gnomad4 ASJ exome

AF:

0.518

Gnomad4 EAS exome

AF:

0.354

Gnomad4 SAS exome

AF:

0.604

Gnomad4 FIN exome

AF:

0.512

Gnomad4 NFE exome

AF:

0.529

Gnomad4 OTH exome

AF:

0.540

GnomAD4 genome

AF:

0.578

AC:

87945

AN:

152130

Hom.:

26251

Cov.:

AF XY:

0.579

AC XY:

43032

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.726

Gnomad4 AMR

AF:

0.539

Gnomad4 ASJ

AF:

0.507

Gnomad4 EAS

AF:

0.340

Gnomad4 SAS

AF:

0.598

Gnomad4 FIN

AF:

0.529

Gnomad4 NFE

AF:

0.526

Gnomad4 OTH

AF:

0.561

Alfa

AF:

0.549

Hom.:

15187

Bravo

AF:

0.584

Asia WGS

AF:

0.545

AC:

1894

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Feb 16, 2016	- -

Hepatoencephalopathy due to combined oxidative phosphorylation defect type 1

Benign:3

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	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. -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Nov 18, 2019	- -

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

6.0

DANN

Benign

0.54

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.3

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over