rs2283839

Positions:

• chr22-26573096-A-C
• chr22-26573096-A-T

Variant summary

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

The NM_003595.5(TPST2):​c.-161+16957T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 151,984 control chromosomes in the GnomAD database, including 14,951 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 0.42 (14951 hom., cov: 32)
• Consequence: TPST2 NM_003595.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0150

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 (EAS) allele frequency at 95% confidence interval = 0.719 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPST2	NM_003595.5	c.-161+16957T>G		intron_variant		ENST00000338754.9	NP_003586.3
TPST2	NM_001362922.2	c.-89+16957T>G		intron_variant			NP_001349851.1
TPST2	NM_001362923.2	c.-118+16957T>G		intron_variant			NP_001349852.1
TPST2	XR_007067981.1	n.80+16957T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPST2	ENST00000338754.9	c.-161+16957T>G		intron_variant		1	NM_003595.5	ENSP00000339813	P1

Frequencies

GnomAD3 genomes AF: 0.423 AC: 64249 AN: 151866 Hom.: 14934 Cov.: 32

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.547

Gnomad ASJ AF: 0.530

Gnomad EAS AF: 0.739

Gnomad SAS AF: 0.714

Gnomad FIN AF: 0.522

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.430

Gnomad OTH AF: 0.466

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

GnomAD4 genome AF: 0.423 AC: 64278 AN: 151984 Hom.: 14951 Cov.: 32 AF XY: 0.436 AC XY: 32412 AN XY: 74292

Gnomad4 AFR AF: 0.257

Gnomad4 AMR AF: 0.548

Gnomad4 ASJ AF: 0.530

Gnomad4 EAS AF: 0.739

Gnomad4 SAS AF: 0.713

Gnomad4 FIN AF: 0.522

Gnomad4 NFE AF: 0.430

Gnomad4 OTH AF: 0.470

Alfa AF: 0.384 Hom.: 2722

Bravo AF: 0.417

Asia WGS AF: 0.709 AC: 2468 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	1.2
DANN	Benign	0.60

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: rs2283839; hg19: chr22-26969061;