12-57796401-C-T

Position:

• chr12-57796401-C-T

Variant summary

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

The NM_005726.6(TSFM):​c.796C>T​(p.Leu266Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,450,156 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TSFM NM_005726.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.922

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]

ENSG00000257921 (HGNC:):

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.796C>T	p.Leu266Phe	missense_variant	6/6	ENST00000652027.2	NP_005717.3
TSFM	NM_001172696.2	c.859C>T	p.Leu287Phe	missense_variant	7/7		NP_001166167.1
TSFM	NM_001172695.2	c.*204C>T		3_prime_UTR_variant	5/5		NP_001166166.1
TSFM	NM_001172697.2	c.571+3328C>T		intron_variant			NP_001166168.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSFM	ENST00000652027.2	c.796C>T	p.Leu266Phe	missense_variant	6/6		NM_005726.6	ENSP00000499171.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000436 AC: 1 AN: 229150 Hom.: 0 AF XY: 0.00000809 AC XY: 1 AN XY: 123564

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000316

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS 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: 0.00000138 AC: 2 AN: 1450156 Hom.: 0 Cov.: 31 AF XY: 0.00000278 AC XY: 2 AN XY: 720300

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000236

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: 9.04e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.016	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T;.
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Benign	0.75	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.043	D
MetaRNN	Uncertain	0.48	T;T
MetaSVM	Uncertain	0.33	D
MutationAssessor	Pathogenic	3.0	M;.
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-2.0	N;N
REVEL	Uncertain	0.50
Sift	Benign	0.057	T;T
Sift4G	Benign	0.10	T;T
Polyphen		0.95	P;D
Vest4		0.24
MutPred		0.50		Gain of catalytic residue at V268 (P = 0);.;
MVP		0.96
MPC		0.36
ClinPred		0.78	D
GERP RS		4.5
Varity_R		0.11
gMVP		0.33

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: rs62000432; hg19: chr12-58190184;