rs709595

chr7-66352346-G-Cchr7-66352346-G-T

Variant summary

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

The NM_003596.4(TPST1):c.1045-159G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 152,066 control chromosomes in the GnomAD database, including 12,866 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 0.41 (12866 hom., cov: 32)
• Consequence: TPST1 NM_003596.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.491

Genes affected

TPST1 (HGNC:12020): (tyrosylprotein sulfotransferase 1) Enables protein homodimerization activity and protein-tyrosine sulfotransferase activity. Involved in peptidyl-tyrosine sulfation. Is integral component of Golgi membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.616 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TPST1	NM_003596.4	c.1045-159G>C		intron_variant		ENST00000304842.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TPST1	ENST00000304842.6	c.1045-159G>C		intron_variant		1	NM_003596.4	P1
TPST1	ENST00000480281.5	n.389-159G>C		intron_variant, non_coding_transcript_variant		1
TPST1	ENST00000649664.1	c.1045-159G>C		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61648 AN: 151948 Hom.: 12858 Cov.: 32

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.527

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.429

Gnomad EAS AF: 0.634

Gnomad SAS AF: 0.545

Gnomad FIN AF: 0.441

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.415

Gnomad OTH AF: 0.429

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

GnomAD4 genome AF: 0.406 AC: 61688 AN: 152066 Hom.: 12866 Cov.: 32 AF XY: 0.409 AC XY: 30434 AN XY: 74326

Gnomad4 AFR AF: 0.319

Gnomad4 AMR AF: 0.438

Gnomad4 ASJ AF: 0.429

Gnomad4 EAS AF: 0.634

Gnomad4 SAS AF: 0.545

Gnomad4 FIN AF: 0.441

Gnomad4 NFE AF: 0.414

Gnomad4 OTH AF: 0.430

Alfa AF: 0.411 Hom.: 1819

Bravo AF: 0.403

Asia WGS AF: 0.592 AC: 2058 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	3.5
Dann	Benign	0.58

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: rs709595; hg19: chr7-65817333; COSMIC: COSV59174692; COSMIC: COSV59174692;