22-37013754-C-T

Variant names:

• chr22-37013754-C-T
• rs470029
• NM_003312.6:c.596-2429G>A

Variant summary

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

The NM_003312.6(TST):​c.596-2429G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0856 in 152,188 control chromosomes in the GnomAD database, including 972 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 0.086 (972 hom., cov: 33)
• Consequence: TST NM_003312.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.399
• Publications: 2 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TST	NM_003312.6	c.596-2429G>A		intron_variant	Intron 2 of 2	ENST00000249042.8	NP_003303.2
TST	NM_001270483.1	c.596-2429G>A		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.596-2429G>A		intron_variant	Intron 2 of 2	1	NM_003312.6	ENSP00000249042.3
TST	ENST00000403892.7	c.596-2429G>A		intron_variant	Intron 1 of 1	1		ENSP00000385828.3
TST	ENST00000622841.1	c.596-2429G>A		intron_variant	Intron 2 of 2	5		ENSP00000478739.1

Frequencies

GnomAD3 genomes AF: 0.0855 AC: 13001 AN: 152070 Hom.: 967 Cov.: 33

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.0534

Gnomad ASJ AF: 0.0424

Gnomad EAS AF: 0.000960

Gnomad SAS AF: 0.0230

Gnomad FIN AF: 0.0390

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0468

Gnomad OTH AF: 0.0718

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

GnomAD4 genome AF: 0.0856 AC: 13032 AN: 152188 Hom.: 972 Cov.: 33 AF XY: 0.0833 AC XY: 6202 AN XY: 74422

African (AFR) AF: 0.197 AC: 8156 AN: 41466

American (AMR) AF: 0.0531 AC: 812 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0424 AC: 147 AN: 3470

East Asian (EAS) AF: 0.000962 AC: 5 AN: 5196

South Asian (SAS) AF: 0.0228 AC: 110 AN: 4830

European-Finnish (FIN) AF: 0.0390 AC: 413 AN: 10602

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0468 AC: 3186 AN: 68016

Other (OTH) AF: 0.0710 AC: 150 AN: 2112

Alfa AF: 0.0590 Hom.: 251

Bravo AF: 0.0920

Asia WGS AF: 0.0230 AC: 79 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.0
DANN	Benign	0.75
PhyloP100		0.40
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: rs470029; hg19: chr22-37409795;