chr22-26524082-T-C

Position:

• chr22-26524082-T-C

Variant summary

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

The NM_003595.5(TPST2):​c.*2193A>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 0.281 in 151,954 control chromosomes in the GnomAD database, including 6,639 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 0.28 (6639 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TPST2 NM_003595.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.148

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 (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TPST2	NM_003595.5	c.*2193A>G		3_prime_UTR_variant	7/7	ENST00000338754.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TPST2	ENST00000338754.9	c.*2193A>G		3_prime_UTR_variant	7/7	1	NM_003595.5	P1
TPST2	ENST00000454778.6	c.*2193A>G		3_prime_UTR_variant	7/7	4		P1

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42683 AN: 151836 Hom.: 6630 Cov.: 32

Gnomad AFR AF: 0.411

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.265

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.281 AC: 42736 AN: 151954 Hom.: 6639 Cov.: 32 AF XY: 0.276 AC XY: 20528 AN XY: 74290

Gnomad4 AFR AF: 0.410

Gnomad4 AMR AF: 0.218

Gnomad4 ASJ AF: 0.228

Gnomad4 EAS AF: 0.193

Gnomad4 SAS AF: 0.130

Gnomad4 FIN AF: 0.271

Gnomad4 NFE AF: 0.240

Gnomad4 OTH AF: 0.264

Alfa AF: 0.241 Hom.: 9324

Bravo AF: 0.286

Asia WGS AF: 0.166 AC: 577 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.59

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: rs3088103; hg19: chr22-26920048;