12-57782812-T-A

Variant names:

• chr12-57782812-T-A
• NM_005726.6:c.11T>A

Variant summary

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

The NM_005726.6(TSFM):​c.11T>A​(p.Leu4Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000694 in 1,440,064 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: 6.9e-7 (0 hom.)
• Consequence: TSFM NM_005726.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17

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 rank	MANE	Protein	UniProt
TSFM	NM_005726.6	c.11T>A	p.Leu4Gln	missense_variant	Exon 1 of 6	ENST00000652027.2	NP_005717.3
TSFM	NM_001172696.2	c.11T>A	p.Leu4Gln	missense_variant	Exon 1 of 7		NP_001166167.1
TSFM	NM_001172697.2	c.11T>A	p.Leu4Gln	missense_variant	Exon 1 of 6		NP_001166168.1
TSFM	NM_001172695.2	c.11T>A	p.Leu4Gln	missense_variant	Exon 1 of 5		NP_001166166.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSFM	ENST00000652027.2	c.11T>A	p.Leu4Gln	missense_variant	Exon 1 of 6		NM_005726.6	ENSP00000499171.2
ENSG00000257921	ENST00000546504.1	c.77-298T>A		intron_variant	Intron 1 of 3	2		ENSP00000449544.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.94e-7 AC: 1 AN: 1440064 Hom.: 0 Cov.: 30 AF XY: 0.00000140 AC XY: 1 AN XY: 714346

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: 9.07e-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	0.084
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T;.;.;.;T;.
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.096	N
LIST_S2	Benign	0.81	T;T;T;T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.47	T;T;T;T;T;T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	1.8	L;L;L;.;.;L
PrimateAI	Uncertain	0.48	T
PROVEAN	Benign	-1.1	N;N;N;N;N;N
REVEL	Benign	0.23
Sift	Uncertain	0.0040	D;D;D;D;D;D
Sift4G	Uncertain	0.0080	D;D;D;D;D;D
Polyphen		0.97	D;.;D;.;.;.
Vest4		0.52
MutPred		0.34		Gain of disorder (P = 0.0199);Gain of disorder (P = 0.0199);Gain of disorder (P = 0.0199);Gain of disorder (P = 0.0199);Gain of disorder (P = 0.0199);Gain of disorder (P = 0.0199);
MVP		0.73
MPC		0.23
ClinPred		0.89	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.36
gMVP		0.69

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.

Other links and lift over

hg19: chr12-58176595;