rs10431552

Positions:

• chr12-57784365-G-A
• chr12-57784365-G-C
• chr12-57784365-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005726.6(TSFM):​c.231+1082G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 152,116 control chromosomes in the GnomAD database, including 7,151 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.28 (7151 hom., cov: 33)
• Consequence: TSFM NM_005726.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.584

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.637 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSFM	NM_005726.6	c.231+1082G>A		intron_variant		ENST00000652027.2
TSFM	NM_001172695.2	c.231+1082G>A		intron_variant
TSFM	NM_001172696.2	c.231+1082G>A		intron_variant
TSFM	NM_001172697.2	c.231+1082G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSFM	ENST00000652027.2	c.231+1082G>A		intron_variant			NM_005726.6	P1

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42146 AN: 151998 Hom.: 7133 Cov.: 33

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.655

Gnomad SAS AF: 0.566

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.249

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.277 AC: 42199 AN: 152116 Hom.: 7151 Cov.: 33 AF XY: 0.286 AC XY: 21300 AN XY: 74360

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.262

Gnomad4 ASJ AF: 0.285

Gnomad4 EAS AF: 0.655

Gnomad4 SAS AF: 0.567

Gnomad4 FIN AF: 0.378

Gnomad4 NFE AF: 0.319

Gnomad4 OTH AF: 0.256

Alfa AF: 0.299 Hom.: 6848

Bravo AF: 0.257

Asia WGS AF: 0.593 AC: 2057 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.90
DANN	Benign	0.15

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: rs10431552; hg19: chr12-58178148;