12-57786286-G-C

Position:

• chr12-57786286-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005726.6(TSFM):​c.355G>C​(p.Val119Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as no classification for the single variant (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TSFM NM_005726.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.72

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSFM	NM_005726.6	c.355G>C	p.Val119Leu	missense_variant	3/6	ENST00000652027.2	NP_005717.3
TSFM	NM_001172696.2	c.355G>C	p.Val119Leu	missense_variant	3/7		NP_001166167.1
TSFM	NM_001172697.2	c.355G>C	p.Val119Leu	missense_variant	3/6		NP_001166168.1
TSFM	NM_001172695.2	c.355G>C	p.Val119Leu	missense_variant	3/5		NP_001166166.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSFM	ENST00000652027.2	c.355G>C	p.Val119Leu	missense_variant	3/6		NM_005726.6	ENSP00000499171	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.47	T;.;.;.;T;.;T;T
Eigen	Uncertain	0.66
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D;D;D;D;D;D;D;D
M_CAP	Benign	0.083	D
MetaRNN	Uncertain	0.73	D;D;D;D;D;D;D;D
MetaSVM	Uncertain	0.071	D
MutationAssessor	Benign	1.9	L;L;L;.;.;L;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;D
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-2.6	D;D;D;D;D;D;D;D
REVEL	Pathogenic	0.65
Sift	Uncertain	0.0060	D;D;D;D;D;D;D;D
Sift4G	Uncertain	0.0080	D;D;D;D;D;D;D;D
Polyphen		0.73	P;.;P;.;.;.;.;.
Vest4		0.69
MutPred		0.59		Gain of catalytic residue at E120 (P = 0.0012);Gain of catalytic residue at E120 (P = 0.0012);Gain of catalytic residue at E120 (P = 0.0012);Gain of catalytic residue at E120 (P = 0.0012);Gain of catalytic residue at E120 (P = 0.0012);Gain of catalytic residue at E120 (P = 0.0012);.;.;
MVP		0.95
MPC		0.35
ClinPred		0.98	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.56
gMVP		0.70

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

LitVar

Other links and lift over

dbSNP: rs863224936; hg19: chr12-58180069;