rs10747783

chr12-57782831-T-Achr12-57782831-T-Cchr12-57782831-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_005726.6(TSFM):c.30T>A(p.Phe10Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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. Synonymous variant affecting the same amino acid position (i.e. F10F) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TSFM NM_005726.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.116

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 Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07937953).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSFM	NM_005726.6	c.30T>A	p.Phe10Leu	missense_variant	1/6	ENST00000652027.2
TSFM	NM_001172696.2	c.30T>A	p.Phe10Leu	missense_variant	1/7
TSFM	NM_001172697.2	c.30T>A	p.Phe10Leu	missense_variant	1/6
TSFM	NM_001172695.2	c.30T>A	p.Phe10Leu	missense_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSFM	ENST00000652027.2	c.30T>A	p.Phe10Leu	missense_variant	1/6		NM_005726.6	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1442500 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 715716

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: 0.00

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	Uncertain	0.38
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
Cadd	Benign	5.1
Dann	Benign	0.91
DEOGEN2	Benign	0.12	T;.;.;.;T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.051	N
LIST_S2	Benign	0.75	T;T;T;T;T;T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.079	T;T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.90	L;L;L;.;.;L
MutationTaster	Benign	1.0	P;P;P;P;P;P;P
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.71	N;N;N;N;N;N
REVEL	Benign	0.018
Sift	Benign	0.046	D;D;D;D;D;D
Sift4G	Benign	0.72	T;T;T;T;T;T
Polyphen		0.0080	B;.;B;.;.;.
Vest4		0.21
MutPred		0.36		Gain of catalytic residue at T15 (P = 0.0028);Gain of catalytic residue at T15 (P = 0.0028);Gain of catalytic residue at T15 (P = 0.0028);Gain of catalytic residue at T15 (P = 0.0028);Gain of catalytic residue at T15 (P = 0.0028);Gain of catalytic residue at T15 (P = 0.0028);
MVP		0.072
MPC		0.081
ClinPred		0.072	T
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.097
gMVP		0.47

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: rs10747783; hg19: chr12-58176614;