rs199599204

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_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. 14/21 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 benign.

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

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

combined oxidative phosphorylation defect type 15
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
Leigh syndrome
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Leigh syndrome with leukodystrophy
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

MTFMT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

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 Benign/Likely_benign. ClinVar VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
MTFMT	NM_139242.4 link	c.16C>T	p.Arg6Trp	missense_variant	Exon 1 of 9	ENST00000220058.9	NP_640335.2
MTFMT	XM_005254158.6 link	c.16C>T	p.Arg6Trp	missense_variant	Exon 1 of 9		XP_005254215.2
MTFMT	XR_001751081.2 link	n.42C>T		non_coding_transcript_exon_variant	Exon 1 of 5
MTFMT	XR_007064421.1 link	n.42C>T		non_coding_transcript_exon_variant	Exon 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTFMT	ENST00000220058.9 link	c.16C>T	p.Arg6Trp	missense_variant	Exon 1 of 9	1	NM_139242.4	ENSP00000220058.4

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

GnomAD2 exomes

AF:

0.00718

AC:

517

AN:

72046

AF XY:

0.00696

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 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

African (AFR)

AF:

0.00144

AC:

AN:

25706

American (AMR)

AF:

0.00298

AC:

AN:

24132

Ashkenazi Jewish (ASJ)

AF:

0.00776

AC:

166

AN:

21404

East Asian (EAS)

AF:

0.00

AC:

AN:

26650

South Asian (SAS)

AF:

0.000329

AC:

AN:

69902

European-Finnish (FIN)

AF:

0.0134

AC:

464

AN:

34596

Middle Eastern (MID)

AF:

0.00448

AC:

AN:

4018

European-Non Finnish (NFE)

AF:

0.0109

AC:

11062

AN:

1019208

Other (OTH)

AF:

0.00688

AC:

357

AN:

51904

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

597

1194

1792

2389

2986

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

430

860

1290

1720

2150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00676

AC:

1028

AN:

151980

Hom.:

Cov.:

AF XY:

0.00666

AC XY:

495

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.00185

AC:

AN:

41534

American (AMR)

AF:

0.00288

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00721

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5098

South Asian (SAS)

AF:

0.000624

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.0124

AC:

131

AN:

10570

Middle Eastern (MID)

AF:

0.00685

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0107

AC:

727

AN:

67894

Other (OTH)

AF:

0.00900

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

103

154

206

257

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

Apr 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

MTFMT: BS1, BS2 -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 09, 2016

Mayo Clinic Laboratories, Mayo Clinic

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Mar 20, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Feb 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Jun 04, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

(source)

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

PhyloP100

1.4

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

PromoterAI

-0.046

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.040

gMVP

0.56

Mutation Taster

=97/3

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over