rs4822739

chr22-26555219-C-Gchr22-26555219-C-T

Variant summary

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

The NM_003595.5(TPST2):c.-160-10544G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0834 in 533,524 control chromosomes in the GnomAD database, including 2,618 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 0.094 (938 hom., cov: 34)
  • Exomes 𝑓: 0.079 (1680 hom.)
• Consequence: TPST2 NM_003595.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.308

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]

MIR548J (HGNC:35276): (microRNA 548j) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TPST2	NM_003595.5	c.-160-10544G>C		intron_variant		ENST00000338754.9
MIR548J	NR_031615.1	n.105G>C		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TPST2	ENST00000338754.9	c.-160-10544G>C		intron_variant		1	NM_003595.5	P1
MIR548J	ENST00000408833.1	n.105G>C		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.0941 AC: 14314 AN: 152178 Hom.: 933 Cov.: 34

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.0749

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.0372

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0492

Gnomad OTH AF: 0.0961

GnomAD3 exomes AF: 0.0877 AC: 21601 AN: 246388 Hom.: 1313 AF XY: 0.0866 AC XY: 11622 AN XY: 134144

Gnomad AFR exome AF: 0.159

Gnomad AMR exome AF: 0.119

Gnomad ASJ exome AF: 0.0748

Gnomad EAS exome AF: 0.208

Gnomad SAS exome AF: 0.128

Gnomad FIN exome AF: 0.0383

Gnomad NFE exome AF: 0.0486

Gnomad OTH exome AF: 0.0726

GnomAD4 exome AF: 0.0791 AC: 30169 AN: 381228 Hom.: 1680 Cov.: 0 AF XY: 0.0823 AC XY: 17875 AN XY: 217134

Gnomad4 AFR exome AF: 0.159

Gnomad4 AMR exome AF: 0.117

Gnomad4 ASJ exome AF: 0.0725

Gnomad4 EAS exome AF: 0.211

Gnomad4 SAS exome AF: 0.128

Gnomad4 FIN exome AF: 0.0383

Gnomad4 NFE exome AF: 0.0490

Gnomad4 OTH exome AF: 0.0740

GnomAD4 genome AF: 0.0941 AC: 14326 AN: 152296 Hom.: 938 Cov.: 34 AF XY: 0.0958 AC XY: 7137 AN XY: 74486

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.0749

Gnomad4 EAS AF: 0.215

Gnomad4 SAS AF: 0.141

Gnomad4 FIN AF: 0.0372

Gnomad4 NFE AF: 0.0492

Gnomad4 OTH AF: 0.0941

Alfa AF: 0.0619 Hom.: 112

Bravo AF: 0.101

Asia WGS AF: 0.152 AC: 532 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.4
Dann	Benign	0.54

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: rs4822739; hg19: chr22-26951185; COSMIC: COSV58680032; COSMIC: COSV58680032;