rs4822743

Variant names:

• chr22-26585075-A-G
• rs4822743
• NM_003595.5:c.-161+4978T>C

Variant summary

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

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003595.5. 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
	TPST2	NM_003595.5	MANE Select	c.-161+4978T>C		intron	N/A	NP_003586.3
	TPST2	NM_001362923.2		c.-118+4978T>C		intron	N/A	NP_001349852.1
	TPST2	NM_001362922.2		c.-89+4978T>C		intron	N/A	NP_001349851.1	O60704

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPST2	ENST00000338754.9	TSL:1 MANE Select	c.-161+4978T>C		intron	N/A	ENSP00000339813.4	O60704
	TPST2	ENST00000910417.1		c.-161+4978T>C		intron	N/A	ENSP00000580476.1
	TPST2	ENST00000403880.5	TSL:5	c.-331+11552T>C		intron	N/A	ENSP00000385192.1	O60704

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

African (AFR) AF: 0.229 AC: 9497 AN: 41496

American (AMR) AF: 0.434 AC: 6631 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.425 AC: 1476 AN: 3472

East Asian (EAS) AF: 0.339 AC: 1754 AN: 5180

South Asian (SAS) AF: 0.427 AC: 2054 AN: 4814

European-Finnish (FIN) AF: 0.360 AC: 3808 AN: 10580

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.364 AC: 24752 AN: 67972

Other (OTH) AF: 0.388 AC: 817 AN: 2108

Alfa AF: 0.365 Hom.: 44044

Bravo AF: 0.341

Asia WGS AF: 0.407 AC: 1419 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.2
DANN	Benign	0.85
PhyloP100		0.53
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: rs4822743; hg19: chr22-26981039;