rs3752523

chr22-26536184-G-A

Variant summary

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

The NM_003595.5(TPST2):c.1041+104C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 1,345,114 control chromosomes in the GnomAD database, including 193,073 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 0.47 (17968 hom., cov: 32)
  • Exomes 𝑓: 0.54 (175105 hom.)
• Consequence: TPST2 NM_003595.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.473

Genes affected

TPST2 (HGNC:12021): (tyrosylprotein sulfotransferase 2) The protein encoded by this gene catalyzes the O-sulfation of tyrosine residues within acidic regions of proteins. The encoded protein is a type II integral membrane protein found in the Golgi body. Alternative splicing produces multiple transcript variants encoding distinct isoforms. [provided by RefSeq, May 2018]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=4.069336E-5).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TPST2	NM_003595.5	c.1041+104C>T		intron_variant		ENST00000338754.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TPST2	ENST00000338754.9	c.1041+104C>T		intron_variant		1	NM_003595.5	P1

Frequencies

GnomAD3 genomes AF: 0.473 AC: 71872 AN: 151824 Hom.: 17966 Cov.: 32

Gnomad AFR AF: 0.338

Gnomad AMI AF: 0.602

Gnomad AMR AF: 0.417

Gnomad ASJ AF: 0.543

Gnomad EAS AF: 0.367

Gnomad SAS AF: 0.391

Gnomad FIN AF: 0.603

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.556

Gnomad OTH AF: 0.479

GnomAD3 exomes AF: 0.481 AC: 79819 AN: 165872 Hom.: 19941 AF XY: 0.484 AC XY: 42633 AN XY: 88044

Gnomad AFR exome AF: 0.336

Gnomad AMR exome AF: 0.356

Gnomad ASJ exome AF: 0.537

Gnomad EAS exome AF: 0.390

Gnomad SAS exome AF: 0.411

Gnomad FIN exome AF: 0.591

Gnomad NFE exome AF: 0.552

Gnomad OTH exome AF: 0.515

GnomAD4 exome AF: 0.536 AC: 639748 AN: 1193172 Hom.: 175105 Cov.: 17 AF XY: 0.533 AC XY: 319749 AN XY: 599356

Gnomad4 AFR exome AF: 0.339

Gnomad4 AMR exome AF: 0.363

Gnomad4 ASJ exome AF: 0.539

Gnomad4 EAS exome AF: 0.352

Gnomad4 SAS exome AF: 0.417

Gnomad4 FIN exome AF: 0.593

Gnomad4 NFE exome AF: 0.565

Gnomad4 OTH exome AF: 0.522

GnomAD4 genome AF: 0.473 AC: 71887 AN: 151942 Hom.: 17968 Cov.: 32 AF XY: 0.472 AC XY: 35053 AN XY: 74274

Gnomad4 AFR AF: 0.338

Gnomad4 AMR AF: 0.416

Gnomad4 ASJ AF: 0.543

Gnomad4 EAS AF: 0.368

Gnomad4 SAS AF: 0.392

Gnomad4 FIN AF: 0.603

Gnomad4 NFE AF: 0.556

Gnomad4 OTH AF: 0.475

Alfa AF: 0.531 Hom.: 31070

Bravo AF: 0.455

TwinsUK AF: 0.551 AC: 2043

ALSPAC AF: 0.556 AC: 2142

ExAC AF: 0.402 AC: 44226

Asia WGS AF: 0.342 AC: 1189 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.57
Cadd	Benign	3.9
Dann	Uncertain	0.98
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.065	N
LIST_S2	Benign	0.32	T
MetaRNN	Benign	0.000041	T
MetaSVM	Benign	-0.94	T
MutationTaster	Benign	1.0	P;P;P
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.0080
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
ClinPred		0.0088	T
GERP RS		-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: rs3752523; hg19: chr22-26932150; COSMIC: COSV58681972;