rs587777419

Variant names:

Variant summary

Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate

The NM_139242.4(MTFMT):c.73C>T(p.Gln25*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000022 in 1,363,614 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

MTFMT
NM_139242.4 stop_gained

Scores

Clinical Significance

Pathogenic criteria provided, single submitter P:2

Conservation

PhyloP100: 0.859

Publications

0 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: Pathogenic. The variant received 12 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 26 pathogenic variants in the truncated region.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 15-65029541-G-A is Pathogenic according to our data. Variant chr15-65029541-G-A is described in ClinVar as Pathogenic. ClinVar VariationId is 133325.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
MTFMT	NM_139242.4 link	c.73C>T	p.Gln25*	stop_gained	Exon 1 of 9	ENST00000220058.9	NP_640335.2
MTFMT	XM_005254158.6 link	c.73C>T	p.Gln25*	stop_gained	Exon 1 of 9		XP_005254215.2
MTFMT	XR_001751081.2 link	n.99C>T		non_coding_transcript_exon_variant	Exon 1 of 5
MTFMT	XR_007064421.1 link	n.99C>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.73C>T	p.Gln25*	stop_gained	Exon 1 of 9	1	NM_139242.4	ENSP00000220058.4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

111566

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

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:

0.00000220

AC:

AN:

1363614

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

671578

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28114

American (AMR)

AF:

0.00

AC:

AN:

32956

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24346

East Asian (EAS)

AF:

0.00

AC:

AN:

32188

South Asian (SAS)

AF:

0.00

AC:

AN:

76146

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43404

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4982

European-Non Finnish (NFE)

AF:

0.00000282

AC:

AN:

1064978

Other (OTH)

AF:

0.00

AC:

AN:

56500

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

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

Cov.:

Alfa

AF:

0.0000331

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Combined oxidative phosphorylation defect type 15

Pathogenic:1

Mar 01, 2014

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

not provided

Pathogenic:1

Dec 20, 2022

GeneDx

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 35772305, 24461907) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.63

BayesDel_noAF

Uncertain

-0.020

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

Eigen

Benign

0.094

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.22

PhyloP100

0.86

Vest4

0.044

GERP RS

1.9

PromoterAI

-0.026

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=10/190

disease causing (ClinVar)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over