Variant 12-57782803-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2

The NM_005726.6(TSFM):c.2T>G(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000239 in 1,590,468 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

TSFM
NM_005726.6 start_lost

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.25

Variant links:

Genes affected

TSFM (HGNC:12367): (Ts translation elongation factor, mitochondrial) This gene encodes a mitochondrial translation elongation factor. The encoded protein is an enzyme that catalyzes the exchange of guanine nucleotides on the translation elongation factor Tu during the elongation step of mitchondrial protein translation. Mutations in this gene are associated with combined oxidative phosphorylation deficiency-3 syndrome. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Mar 2010]

TSFM links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 10 ACMG points.

PVS1

Start lost variant, no new inframe start found.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TSFM	NM_005726.6 linkuse as main transcript	c.2T>G	p.Met1?	start_lost	1/6	ENST00000652027.2	NP_005717.3
TSFM	NM_001172696.2 linkuse as main transcript	c.2T>G	p.Met1?	start_lost	1/7		NP_001166167.1
TSFM	NM_001172697.2 linkuse as main transcript	c.2T>G	p.Met1?	start_lost	1/6		NP_001166168.1
TSFM	NM_001172695.2 linkuse as main transcript	c.2T>G	p.Met1?	start_lost	1/5		NP_001166166.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSFM	ENST00000652027.2 linkuse as main transcript	c.2T>G	p.Met1?	start_lost	1/6		NM_005726.6	ENSP00000499171	P1	P43897-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000257

AC:

AN:

1438264

Hom.:

Cov.:

AF XY:

0.0000308

AC XY:

AN XY:

713222

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000327

Gnomad4 OTH exome

AF:

0.0000168

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Skeletal myopathy

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Blueprint Genetics

Oct 12, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.63

BayesDel_noAF

Pathogenic

0.40

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Benign

0.13

T;.;.;.;T;.

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Benign

0.66

LIST_S2

Uncertain

0.90

D;D;D;D;D;D

M_CAP

Pathogenic

0.46

MetaRNN

Pathogenic

0.99

D;D;D;D;D;D

MetaSVM

Uncertain

-0.18

MutationTaster

Benign

1.0

D;D;D;D;D;D;D

PROVEAN

Benign

-1.2

N;N;N;N;N;N

REVEL

Uncertain

0.47

Sift

Pathogenic

0.0

D;D;D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D;D;D

Polyphen

0.99

D;.;P;.;.;.

Vest4

0.94

MutPred

0.95

Gain of disorder (P = 0.0187);Gain of disorder (P = 0.0187);Gain of disorder (P = 0.0187);Gain of disorder (P = 0.0187);Gain of disorder (P = 0.0187);Gain of disorder (P = 0.0187);

MVP

0.66

ClinPred

1.0

GERP RS

4.7

Varity_R

0.98

gMVP

0.85

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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