chr7-66352346-G-C

Variant names:

• chr7-66352346-G-C
• rs709595
• NM_003596.4:c.1045-159G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003596.4. 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
	TPST1	NM_003596.4	MANE Select	c.1045-159G>C		intron	N/A	NP_003587.1	O60507

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPST1	ENST00000304842.6	TSL:1 MANE Select	c.1045-159G>C		intron	N/A	ENSP00000302413.5	O60507
	TPST1	ENST00000480281.5	TSL:1	n.389-159G>C		intron	N/A
	TPST1	ENST00000649664.1		c.1045-159G>C		intron	N/A	ENSP00000497281.1	O60507

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

African (AFR) AF: 0.319 AC: 13228 AN: 41490

American (AMR) AF: 0.438 AC: 6687 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.429 AC: 1487 AN: 3470

East Asian (EAS) AF: 0.634 AC: 3271 AN: 5158

South Asian (SAS) AF: 0.545 AC: 2628 AN: 4826

European-Finnish (FIN) AF: 0.441 AC: 4659 AN: 10566

Middle Eastern (MID) AF: 0.572 AC: 167 AN: 292

European-Non Finnish (NFE) AF: 0.414 AC: 28174 AN: 67974

Other (OTH) AF: 0.430 AC: 907 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.5
DANN	Benign	0.58
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: rs709595; hg19: chr7-65817333; COSMIC: COSV59174692; COSMIC: COSV59174692;