12-57786633-G-C

Variant names:

• chr12-57786633-G-C
• rs724834
• NM_005726.6:c.360+342G>C

Variant summary

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

The NM_005726.6(TSFM):​c.360+342G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 152,168 control chromosomes in the GnomAD database, including 6,794 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 0.27 (6794 hom., cov: 32)
• Consequence: TSFM NM_005726.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.325

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSFM	NM_005726.6	c.360+342G>C		intron_variant	Intron 3 of 5	ENST00000652027.2	NP_005717.3
TSFM	NM_001172696.2	c.360+342G>C		intron_variant	Intron 3 of 6		NP_001166167.1
TSFM	NM_001172697.2	c.360+342G>C		intron_variant	Intron 3 of 5		NP_001166168.1
TSFM	NM_001172695.2	c.360+342G>C		intron_variant	Intron 3 of 4		NP_001166166.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSFM	ENST00000652027.2	c.360+342G>C		intron_variant	Intron 3 of 5		NM_005726.6	ENSP00000499171.2

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40407 AN: 152050 Hom.: 6792 Cov.: 32

Gnomad AFR AF: 0.0793

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.651

Gnomad SAS AF: 0.497

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.239

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

GnomAD4 genome AF: 0.266 AC: 40414 AN: 152168 Hom.: 6794 Cov.: 32 AF XY: 0.274 AC XY: 20384 AN XY: 74386

Gnomad4 AFR AF: 0.0791

Gnomad4 AMR AF: 0.256

Gnomad4 ASJ AF: 0.286

Gnomad4 EAS AF: 0.651

Gnomad4 SAS AF: 0.498

Gnomad4 FIN AF: 0.378

Gnomad4 NFE AF: 0.317

Gnomad4 OTH AF: 0.237

Alfa AF: 0.166 Hom.: 366

Bravo AF: 0.247

Asia WGS AF: 0.519 AC: 1802 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.4
DANN	Benign	0.68

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: rs724834; hg19: chr12-58180416;