15-65029598-G-C

Position:

chr15-65029598-G-C

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 2P and 20B. PM5BP4_StrongBP6_Very_StrongBS1BS2

The NM_139242.4(MTFMT):c.16C>G(p.Arg6Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000406 in 1,429,532 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R6P) has been classified as Likely pathogenic.

Frequency

Genomes: 𝑓 0.0023 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00018 ( 1 hom. )

Consequence

MTFMT
NM_139242.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.40

Variant links:

Genes affected

MTFMT (HGNC:29666): (mitochondrial methionyl-tRNA formyltransferase) The protein encoded by this nuclear gene localizes to the mitochondrion, where it catalyzes the formylation of methionyl-tRNA. [provided by RefSeq, Jun 2011]

MTFMT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

PM5

Other missense variant is known to change same aminoacid residue: Variant chr15-65029597-C-G is described in Lovd as [Likely_pathogenic].

BP4

Computational evidence support a benign effect (MetaRNN=0.006596297).

BP6

Variant 15-65029598-G-C is Benign according to our data. Variant chr15-65029598-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 669075.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 = 0.0023 (350/151986) while in subpopulation AFR AF= 0.00814 (338/41534). AF 95% confidence interval is 0.00742. There are 2 homozygotes in gnomad4. There are 169 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTFMT	NM_139242.4 link	c.16C>G	p.Arg6Gly	missense_variant	1/9	ENST00000220058.9	NP_640335.2	Q96DP5-1
MTFMT	XM_005254158.6 link	c.16C>G	p.Arg6Gly	missense_variant	1/9		XP_005254215.2
MTFMT	XR_001751081.2 link	n.42C>G		non_coding_transcript_exon_variant	1/5
MTFMT	XR_007064421.1 link	n.42C>G		non_coding_transcript_exon_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTFMT	ENST00000220058.9 link	c.16C>G	p.Arg6Gly	missense_variant	1/9	1	NM_139242.4	ENSP00000220058.4		Q96DP5-1

Frequencies

GnomAD3 genomes

AF:

0.00229

AC:

348

AN:

151876

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00811

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

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:

0.00

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.0000833

AC:

AN:

72046

Hom.:

AF XY:

0.0000720

AC XY:

AN XY:

41690

show subpopulations

Gnomad AFR exome

AF:

0.00683

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000180

AC:

230

AN:

1277546

Hom.:

Cov.:

AF XY:

0.000157

AC XY:

AN XY:

625938

show subpopulations

Gnomad4 AFR exome

AF:

0.00797

Gnomad4 AMR exome

AF:

0.0000414

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000143

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.81e-7

Gnomad4 OTH exome

AF:

0.000405

GnomAD4 genome

AF:

0.00230

AC:

350

AN:

151986

Hom.:

Cov.:

AF XY:

0.00227

AC XY:

169

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.00814

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.0000788

Hom.:

Bravo

AF:

0.00252

ExAC

AF:

0.0000448

AC:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 17, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 13, 2020	- -

MTFMT-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 05, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.19

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.25

M_CAP

Benign

0.044

MetaRNN

Benign

0.0066

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.7

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.91

REVEL

Benign

0.28

Sift

Uncertain

0.020

Sift4G

Pathogenic

0.0

Polyphen

0.0060

Vest4

0.37

MVP

0.52

MPC

0.21

ClinPred

0.015

GERP RS

0.48

Varity_R

0.077

gMVP

0.57

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