3-158644562-C-T

Position:

chr3-158644562-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_024996.7(GFM1):c.-73C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0028 in 1,280,288 control chromosomes in the GnomAD database, including 80 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 50 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 30 hom. )

Consequence

GFM1
NM_024996.7 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.170

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 3-158644562-C-T is Benign according to our data. Variant chr3-158644562-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 343917.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0128 (1955/152324) while in subpopulation AFR AF= 0.0448 (1861/41572). AF 95% confidence interval is 0.0431. There are 50 homozygotes in gnomad4. There are 947 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 50 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GFM1	NM_024996.7 linkuse as main transcript	c.-73C>T		5_prime_UTR_variant	1/18	ENST00000486715.6	NP_079272.4

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GFM1	ENST00000486715.6 linkuse as main transcript	c.-73C>T	5_prime_UTR_variant	1/18	1	NM_024996.7	ENSP00000419038	P1	Q96RP9-1
GFM1	ENST00000478576.5 linkuse as main transcript	c.-73C>T	5_prime_UTR_variant	1/14	2		ENSP00000418755
GFM1	ENST00000478254.5 linkuse as main transcript	c.-73C>T	5_prime_UTR_variant, NMD_transcript_variant	1/18	5		ENSP00000417225
GFM1	ENST00000264263.9 linkuse as main transcript		upstream_gene_variant		5		ENSP00000264263		Q96RP9-2

Frequencies

GnomAD3 genomes

AF:

0.0128

AC:

1947

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0447

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00353

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.0100

GnomAD4 exome

AF:

0.00145

AC:

1633

AN:

1127964

Hom.:

Cov.:

AF XY:

0.00130

AC XY:

736

AN XY:

566654

show subpopulations

Gnomad4 AFR exome

AF:

0.0437

Gnomad4 AMR exome

AF:

0.00322

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000684

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000240

Gnomad4 OTH exome

AF:

0.00392

GnomAD4 genome

AF:

0.0128

AC:

1955

AN:

152324

Hom.:

Cov.:

AF XY:

0.0127

AC XY:

947

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.0448

Gnomad4 AMR

AF:

0.00353

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000279

Gnomad4 OTH

AF:

0.00994

Alfa

AF:

0.000541

Hom.:

Bravo

AF:

0.0142

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hepatoencephalopathy due to combined oxidative phosphorylation defect type 1

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

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. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

8.4

DANN

Benign

0.83

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

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