22-37011486-T-C

Variant names:

• chr22-37011486-T-C
• rs5756477
• NM_003312.6:c.596-161A>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.596-161A>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
• Publications: 9 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003312.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TST	NM_003312.6	MANE Select	c.596-161A>G		intron	N/A	NP_003303.2
	TST	NM_001270483.1		c.596-161A>G		intron	N/A	NP_001257412.1	A0A384NKQ2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TST	ENST00000249042.8	TSL:1 MANE Select	c.596-161A>G		intron	N/A	ENSP00000249042.3	Q16762
	TST	ENST00000403892.7	TSL:1	c.596-161A>G		intron	N/A	ENSP00000385828.3	Q16762
	TST	ENST00000864752.1		c.659-161A>G		intron	N/A	ENSP00000534811.1

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

African (AFR) AF: 0.482 AC: 19951 AN: 41418

American (AMR) AF: 0.461 AC: 7040 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.566 AC: 1965 AN: 3470

East Asian (EAS) AF: 0.518 AC: 2675 AN: 5160

South Asian (SAS) AF: 0.404 AC: 1950 AN: 4822

European-Finnish (FIN) AF: 0.426 AC: 4507 AN: 10572

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.471 AC: 32005 AN: 67950

Other (OTH) AF: 0.500 AC: 1059 AN: 2116

Alfa AF: 0.475 Hom.: 71617

Bravo AF: 0.478

Asia WGS AF: 0.440 AC: 1534 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.0
DANN	Benign	0.53
PhyloP100		-0.49
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: rs5756477; hg19: chr22-37407527;