Variant rs4822739 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.308

Variant links:

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]

TPST2 links:

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]

MIR548J links:

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ACMG classification

Classification made for transcript

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	Protein	UniProt
TPST2	NM_003595.5 linkuse as main transcript	c.-160-10544G>C		intron_variant		ENST00000338754.9	NP_003586.3
MIR548J	NR_031615.1 linkuse as main transcript	n.105G>C		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPST2	ENST00000338754.9 linkuse as main transcript	c.-160-10544G>C		intron_variant		1	NM_003595.5	ENSP00000339813	P1
MIR548J	ENST00000408833.1 linkuse as main transcript	n.105G>C		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.0941

AC:

14314

AN:

152178

Hom.:

933

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0823

AC XY:

17875

AN XY:

217134

show subpopulations

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.:

AF XY:

0.0958

AC XY:

7137

AN XY:

74486

show subpopulations

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over