chr22-37011486-T-C

Variant names:

• chr22-37011486-T-C
• rs5756477
• NM_003312.6:c.596-161A>G

Variant summary

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

The NM_003312.6(TST):​c.596-161A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 151,986 control chromosomes in the GnomAD database, including 17,001 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 0.47 (17001 hom., cov: 32)
• Consequence: TST NM_003312.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.494

Genes affected

TST (HGNC:12388): (thiosulfate sulfurtransferase) This is one of two neighboring genes encoding similar proteins that each contain two rhodanese domains. The encoded protein is localized to the mitochondria and catalyzes the conversion of thiosulfate and cyanide to thiocyanate and sulfite. In addition, the protein interacts with 5S ribosomal RNA and facilitates its import into the mitochondria. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TST	NM_003312.6	c.596-161A>G		intron_variant	Intron 2 of 2	ENST00000249042.8	NP_003303.2
TST	NM_001270483.1	c.596-161A>G		intron_variant	Intron 2 of 2		NP_001257412.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TST	ENST00000249042.8	c.596-161A>G		intron_variant	Intron 2 of 2	1	NM_003312.6	ENSP00000249042.3
TST	ENST00000403892.7	c.596-161A>G		intron_variant	Intron 1 of 1	1		ENSP00000385828.3
TST	ENST00000622841.1	c.596-161A>G		intron_variant	Intron 2 of 2	5		ENSP00000478739.1

Frequencies

GnomAD3 genomes AF: 0.472 AC: 71715 AN: 151868 Hom.: 16995 Cov.: 32

Gnomad AFR AF: 0.482

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.566

Gnomad EAS AF: 0.519

Gnomad SAS AF: 0.405

Gnomad FIN AF: 0.426

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.471

Gnomad OTH AF: 0.502

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

GnomAD4 genome AF: 0.472 AC: 71766 AN: 151986 Hom.: 17001 Cov.: 32 AF XY: 0.470 AC XY: 34891 AN XY: 74296

Gnomad4 AFR AF: 0.482

Gnomad4 AMR AF: 0.461

Gnomad4 ASJ AF: 0.566

Gnomad4 EAS AF: 0.518

Gnomad4 SAS AF: 0.404

Gnomad4 FIN AF: 0.426

Gnomad4 NFE AF: 0.471

Gnomad4 OTH AF: 0.500

Alfa AF: 0.475 Hom.: 33812

Bravo AF: 0.478

Asia WGS AF: 0.440 AC: 1534 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.0
DANN	Benign	0.53

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: rs5756477; hg19: chr22-37407527;