15-65029598-G-C

Variant names:

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>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. 16/22 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 0.0023 ( 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

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=0.006596297).

BP6

Variant 15-65029598-G-C is Benign according to our data. Variant chr15-65029598-G-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139242.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTFMT	NM_139242.4	MANE Select	c.16C>G	p.Arg6Gly	missense	Exon 1 of 9	NP_640335.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MTFMT	ENST00000220058.9	TSL:1 MANE Select	c.16C>G	p.Arg6Gly	missense	Exon 1 of 9	ENSP00000220058.4
MTFMT	ENST00000543678.1	TSL:2	n.16C>G		non_coding_transcript_exon	Exon 1 of 4	ENSP00000443754.1
MTFMT	ENST00000558460.5	TSL:5	n.16C>G		non_coding_transcript_exon	Exon 1 of 10	ENSP00000452646.1

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

GnomAD2 exomes

AF:

0.0000833

AC:

AN:

72046

AF XY:

0.0000720

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 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

African (AFR)

AF:

0.00797

AC:

205

AN:

25706

American (AMR)

AF:

0.0000414

AC:

AN:

24132

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21404

East Asian (EAS)

AF:

0.00

AC:

AN:

26650

South Asian (SAS)

AF:

0.0000143

AC:

AN:

69902

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34600

Middle Eastern (MID)

AF:

0.000249

AC:

AN:

4018

European-Non Finnish (NFE)

AF:

9.81e-7

AC:

AN:

1019228

Other (OTH)

AF:

0.000405

AC:

AN:

51906

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.00230

AC:

350

AN:

151986

Hom.:

Cov.:

AF XY:

0.00227

AC XY:

169

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.00814

AC:

338

AN:

41534

American (AMR)

AF:

0.000654

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5098

South Asian (SAS)

AF:

0.00

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10572

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67898

Other (OTH)

AF:

0.000948

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000788

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

Apr 08, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jan 13, 2020

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

MTFMT-related disorder

Benign:1

Aug 05, 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 v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.23

CADD

Benign

(source)

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

PhyloP100

1.4

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

PromoterAI

-0.25

Neutral

(source)

Varity_R

0.077

gMVP

0.57

Mutation Taster

=99/1

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over