22-37012094-T-C

Position:

• chr22-37012094-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.93).
• 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/exons	MANE	Protein	UniProt
TST	NM_003312.6	c.596-769A>G		intron_variant		ENST00000249042.8	NP_003303.2
TST	NM_001270483.1	c.596-769A>G		intron_variant			NP_001257412.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TST	ENST00000249042.8	c.596-769A>G		intron_variant		1	NM_003312.6	ENSP00000249042	P1
TST	ENST00000403892.7	c.596-769A>G		intron_variant		1		ENSP00000385828	P1
TST	ENST00000622841.1	c.596-769A>G		intron_variant		5		ENSP00000478739	P1

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

Gnomad4 AFR AF: 0.780

Gnomad4 AMR AF: 0.606

Gnomad4 ASJ AF: 0.635

Gnomad4 EAS AF: 0.524

Gnomad4 SAS AF: 0.487

Gnomad4 FIN AF: 0.504

Gnomad4 NFE AF: 0.552

Gnomad4 OTH AF: 0.626

Alfa AF: 0.587 Hom.: 11703

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

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: rs130598; hg19: chr22-37408135;