rs4822743

Positions:

• chr22-26585075-A-G

Variant summary

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

The NM_003595.5(TPST2):​c.-161+4978T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 152,104 control chromosomes in the GnomAD database, including 9,054 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 0.34 (9054 hom., cov: 33)
• Consequence: TPST2 NM_003595.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.526

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.425 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TPST2	NM_003595.5	c.-161+4978T>C		intron_variant		ENST00000338754.9
TPST2	NM_001362922.2	c.-89+4978T>C		intron_variant
TPST2	NM_001362923.2	c.-118+4978T>C		intron_variant
TPST2	XR_007067981.1	n.80+4978T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TPST2	ENST00000338754.9	c.-161+4978T>C		intron_variant		1	NM_003595.5	P1

Frequencies

GnomAD3 genomes AF: 0.336 AC: 51084 AN: 151986 Hom.: 9035 Cov.: 33

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.433

Gnomad ASJ AF: 0.425

Gnomad EAS AF: 0.339

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.360

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.364

Gnomad OTH AF: 0.385

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

GnomAD4 genome AF: 0.336 AC: 51147 AN: 152104 Hom.: 9054 Cov.: 33 AF XY: 0.339 AC XY: 25196 AN XY: 74364

Gnomad4 AFR AF: 0.229

Gnomad4 AMR AF: 0.434

Gnomad4 ASJ AF: 0.425

Gnomad4 EAS AF: 0.339

Gnomad4 SAS AF: 0.427

Gnomad4 FIN AF: 0.360

Gnomad4 NFE AF: 0.364

Gnomad4 OTH AF: 0.388

Alfa AF: 0.375 Hom.: 22582

Bravo AF: 0.341

Asia WGS AF: 0.407 AC: 1419 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.2
DANN	Benign	0.85

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: rs4822743; hg19: chr22-26981039;