7-66360270-T-G

Variant names:

• chr7-66360270-T-G
• rs3757417
• NM_003596.4:c.*405T>G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_003596.4(TPST1):​c.*405T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0977 in 218,352 control chromosomes in the GnomAD database, including 1,274 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 0.091 (803 hom., cov: 32)
  • Exomes 𝑓: 0.11 (471 hom.)
• Consequence: TPST1 NM_003596.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.75

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPST1	NM_003596.4	c.*405T>G		3_prime_UTR_variant	Exon 6 of 6	ENST00000304842.6	NP_003587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPST1	ENST00000304842.6	c.*405T>G		3_prime_UTR_variant	Exon 6 of 6	1	NM_003596.4	ENSP00000302413.5
TPST1	ENST00000649664.1	c.*405T>G		3_prime_UTR_variant	Exon 7 of 7			ENSP00000497281.1
TPST1	ENST00000490159.1	n.99+3399T>G		intron_variant	Intron 2 of 2	5

Frequencies

GnomAD3 genomes AF: 0.0913 AC: 13886 AN: 152142 Hom.: 801 Cov.: 32

Gnomad AFR AF: 0.0216

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.0785

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.0965

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.0914

GnomAD4 exome AF: 0.113 AC: 7436 AN: 66092 Hom.: 471 Cov.: 0 AF XY: 0.111 AC XY: 3824 AN XY: 34354

Gnomad4 AFR exome AF: 0.0212

Gnomad4 AMR exome AF: 0.0806

Gnomad4 ASJ exome AF: 0.188

Gnomad4 EAS exome AF: 0.0968

Gnomad4 SAS exome AF: 0.105

Gnomad4 FIN exome AF: 0.162

Gnomad4 NFE exome AF: 0.116

Gnomad4 OTH exome AF: 0.119

GnomAD4 genome AF: 0.0912 AC: 13888 AN: 152260 Hom.: 803 Cov.: 32 AF XY: 0.0929 AC XY: 6914 AN XY: 74428

Gnomad4 AFR AF: 0.0216

Gnomad4 AMR AF: 0.0783

Gnomad4 ASJ AF: 0.193

Gnomad4 EAS AF: 0.112

Gnomad4 SAS AF: 0.0966

Gnomad4 FIN AF: 0.161

Gnomad4 NFE AF: 0.119

Gnomad4 OTH AF: 0.0928

Alfa AF: 0.109 Hom.: 1363

Bravo AF: 0.0825

Asia WGS AF: 0.0910 AC: 316 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	13
DANN	Benign	0.89

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: rs3757417; hg19: chr7-65825257;