chr22-37012094-T-C

Variant names:

• chr22-37012094-T-C
• rs130598
• NM_003312.6:c.596-769A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003312.6(TST):​c.596-769A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.616 in 152,084 control chromosomes in the GnomAD database, including 29,853 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 0.62 (29853 hom., cov: 33)
• Consequence: TST NM_003312.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.79
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.773 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TST	NM_003312.6	c.596-769A>G		intron_variant	Intron 2 of 2	ENST00000249042.8	NP_003303.2
TST	NM_001270483.1	c.596-769A>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.596-769A>G		intron_variant	Intron 2 of 2	1	NM_003312.6	ENSP00000249042.3
TST	ENST00000403892.7	c.596-769A>G		intron_variant	Intron 1 of 1	1		ENSP00000385828.3
TST	ENST00000622841.1	c.596-769A>G		intron_variant	Intron 2 of 2	5		ENSP00000478739.1

Frequencies

GnomAD3 genomes AF: 0.616 AC: 93663 AN: 151966 Hom.: 29821 Cov.: 33

Gnomad AFR AF: 0.780

Gnomad AMI AF: 0.601

Gnomad AMR AF: 0.606

Gnomad ASJ AF: 0.635

Gnomad EAS AF: 0.524

Gnomad SAS AF: 0.487

Gnomad FIN AF: 0.504

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.551

Gnomad OTH AF: 0.630

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

GnomAD4 genome AF: 0.616 AC: 93751 AN: 152084 Hom.: 29853 Cov.: 33 AF XY: 0.611 AC XY: 45449 AN XY: 74334

African (AFR) AF: 0.780 AC: 32377 AN: 41524

American (AMR) AF: 0.606 AC: 9258 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.635 AC: 2200 AN: 3464

East Asian (EAS) AF: 0.524 AC: 2706 AN: 5164

South Asian (SAS) AF: 0.487 AC: 2342 AN: 4810

European-Finnish (FIN) AF: 0.504 AC: 5322 AN: 10554

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.552 AC: 37486 AN: 67964

Other (OTH) AF: 0.626 AC: 1325 AN: 2116

Alfa AF: 0.590 Hom.: 13878

Bravo AF: 0.637

Asia WGS AF: 0.498 AC: 1734 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.23
DANN	Benign	0.28
PhyloP100		-2.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs130598; hg19: chr22-37408135;