rs199599204

Positions:

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>T(p.Arg6Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00925 in 1,429,500 control chromosomes in the GnomAD database, including 80 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 0.0068 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0095 ( 76 hom. )

Consequence

MTFMT
NM_139242.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

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=0.0064000785).

BP6

Variant 15-65029598-G-A is Benign according to our data. Variant chr15-65029598-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 374493.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00676 (1028/151980) while in subpopulation NFE AF= 0.0107 (727/67894). AF 95% confidence interval is 0.0101. There are 4 homozygotes in gnomad4. There are 495 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MTFMT	NM_139242.4 linkuse as main transcript	c.16C>T	p.Arg6Trp	missense_variant	1/9	ENST00000220058.9	NP_640335.2
MTFMT	XM_005254158.6 linkuse as main transcript	c.16C>T	p.Arg6Trp	missense_variant	1/9		XP_005254215.2
MTFMT	XR_001751081.2 linkuse as main transcript	n.42C>T		non_coding_transcript_exon_variant	1/5
MTFMT	XR_007064421.1 linkuse as main transcript	n.42C>T		non_coding_transcript_exon_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTFMT	ENST00000220058.9 linkuse as main transcript	c.16C>T	p.Arg6Trp	missense_variant	1/9	1	NM_139242.4	ENSP00000220058	P1	Q96DP5-1

Frequencies

GnomAD3 genomes

AF:

0.00678

AC:

1030

AN:

151870

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00186

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00295

Gnomad ASJ

AF:

0.00721

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000623

Gnomad FIN

AF:

0.0124

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.0107

Gnomad OTH

AF:

0.00910

GnomAD3 exomes

AF:

0.00718

AC:

517

AN:

72046

Hom.:

AF XY:

0.00696

AC XY:

290

AN XY:

41690

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00266

Gnomad ASJ exome

AF:

0.00885

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000583

Gnomad FIN exome

AF:

0.0110

Gnomad NFE exome

AF:

0.0130

Gnomad OTH exome

AF:

0.00583

GnomAD4 exome

AF:

0.00955

AC:

12199

AN:

1277520

Hom.:

Cov.:

AF XY:

0.00915

AC XY:

5725

AN XY:

625926

show subpopulations

Gnomad4 AFR exome

AF:

0.00144

Gnomad4 AMR exome

AF:

0.00298

Gnomad4 ASJ exome

AF:

0.00776

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000329

Gnomad4 FIN exome

AF:

0.0134

Gnomad4 NFE exome

AF:

0.0109

Gnomad4 OTH exome

AF:

0.00688

GnomAD4 genome

AF:

0.00676

AC:

1028

AN:

151980

Hom.:

Cov.:

AF XY:

0.00666

AC XY:

495

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.00185

Gnomad4 AMR

AF:

0.00288

Gnomad4 ASJ

AF:

0.00721

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000624

Gnomad4 FIN

AF:

0.0124

Gnomad4 NFE

AF:

0.0107

Gnomad4 OTH

AF:

0.00900

Alfa

AF:

0.00335

Hom.:

Bravo

AF:

0.00617

ESP6500AA

AF:

0.00233

AC:

ESP6500EA

AF:

0.00914

AC:

ExAC

AF:

0.00348

AC:

233

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Mar 20, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	- -
Likely benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Mar 09, 2016	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2024	MTFMT: BS1, BS2 -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 12, 2018

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. -

MTFMT-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 04, 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

0.33

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.22

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.20

MetaRNN

Benign

0.0064

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.7

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-1.6

REVEL

Benign

0.25

Sift

Uncertain

0.0040

Sift4G

Pathogenic

0.0

Polyphen

0.029

Vest4

0.15

MVP

0.54

MPC

0.31

ClinPred

0.049

GERP RS

0.48

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.040

gMVP

0.56

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