Genetic Variant NM_005726.6:c.22C>A (chr12-57782823-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 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. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

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

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:

ENSG00000257921 (HGNC:):

ENSG00000257921 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSFM	NM_005726.6 link	c.22C>A	p.Arg8Ser	missense_variant	Exon 1 of 6	ENST00000652027.2	NP_005717.3	P43897-1E5KS95
TSFM	NM_001172696.2 link	c.22C>A	p.Arg8Ser	missense_variant	Exon 1 of 7		NP_001166167.1	P43897-2
TSFM	NM_001172697.2 link	c.22C>A	p.Arg8Ser	missense_variant	Exon 1 of 6		NP_001166168.1	P43897-4
TSFM	NM_001172695.2 link	c.22C>A	p.Arg8Ser	missense_variant	Exon 1 of 5		NP_001166166.1	P43897-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSFM	ENST00000652027.2 link	c.22C>A	p.Arg8Ser	missense_variant	Exon 1 of 6		NM_005726.6	ENSP00000499171.2		P43897-1
ENSG00000257921	ENST00000546504.1 link	c.77-287C>A		intron_variant	Intron 1 of 3	2		ENSP00000449544.1		H0YIJ7

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

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:

9.06e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

0.0023

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.14

T;.;.;.;T;.

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.75

T;T;T;T;T;T

M_CAP

Benign

0.0061

MetaRNN

Benign

0.13

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;L;L;.;.;L

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.0

N;N;N;N;N;N

REVEL

Benign

0.20

Sift

Pathogenic

0.0

D;D;D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D;D;D

Polyphen

0.0040

B;.;P;.;.;.

Vest4

0.26

MutPred

0.43

Loss of MoRF binding (P = 0.0221);Loss of MoRF binding (P = 0.0221);Loss of MoRF binding (P = 0.0221);Loss of MoRF binding (P = 0.0221);Loss of MoRF binding (P = 0.0221);Loss of MoRF binding (P = 0.0221);

MVP

0.19

MPC

0.063

ClinPred

0.77

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.20

gMVP

0.79

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over