rs755773165

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005726.6(TSFM):c.22C>A(p.Arg8Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000693 in 1,442,944 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R8C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

TSFM
NM_005726.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.19

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

mitochondrial disease
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
fatal mitochondrial disease due to combined oxidative phosphorylation defect type 3
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
Leigh syndrome
Inheritance: AR Classification: MODERATE Submitted by: ClinGen

TSFM links:

ENSG00000257921 (HGNC:):

ENSG00000257921 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1341548).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005726.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TSFM	NM_005726.6	MANE Select	c.22C>A	p.Arg8Ser	missense	Exon 1 of 6	NP_005717.3
TSFM	NM_001172696.2		c.22C>A	p.Arg8Ser	missense	Exon 1 of 7	NP_001166167.1	P43897-2
TSFM	NM_001172697.2		c.22C>A	p.Arg8Ser	missense	Exon 1 of 6	NP_001166168.1	P43897-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TSFM	ENST00000652027.2	MANE Select	c.22C>A	p.Arg8Ser	missense	Exon 1 of 6	ENSP00000499171.2	P43897-1
TSFM	ENST00000323833.12	TSL:1	c.22C>A	p.Arg8Ser	missense	Exon 1 of 7	ENSP00000313877.8	P43897-2
TSFM	ENST00000543727.5	TSL:1	c.22C>A	p.Arg8Ser	missense	Exon 1 of 6	ENSP00000439342.1	P43897-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.93e-7

AC:

AN:

1442944

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

716126

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33066

American (AMR)

AF:

0.00

AC:

AN:

41986

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25730

East Asian (EAS)

AF:

0.00

AC:

AN:

38550

South Asian (SAS)

AF:

0.00

AC:

AN:

83116

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51378

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5738

European-Non Finnish (NFE)

AF:

9.06e-7

AC:

AN:

1103754

Other (OTH)

AF:

0.00

AC:

AN:

59626

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

0.0023

BayesDel_noAF

Benign

-0.23

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.14

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.75

M_CAP

Benign

0.0061

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

PhyloP100

1.2

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.0

REVEL

Benign

0.20

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.0040

Vest4

0.26

MutPred

0.43

Loss of MoRF binding (P = 0.0221)

MVP

0.19

MPC

0.063

ClinPred

0.77

GERP RS

4.1

PromoterAI

0.057

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.20

gMVP

0.79

Mutation Taster

=87/13

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over