dbSNP rs12161068: TPST2:c.-160-10574A>G (chr22-26555249-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003595.5(TPST2):c.-160-10574A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0102 in 531,774 control chromosomes in the GnomAD database, including 227 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 0.027 ( 171 hom., cov: 34)

Exomes 𝑓: 0.0036 ( 56 hom. )

Consequence

TPST2
NM_003595.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.308

Publications

4 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0899 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPST2	NM_003595.5 link	c.-160-10574A>G		intron_variant	Intron 1 of 6	ENST00000338754.9	NP_003586.3	O60704A0A024R1G9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPST2	ENST00000338754.9 link	c.-160-10574A>G		intron_variant	Intron 1 of 6	1	NM_003595.5	ENSP00000339813.4		O60704

Frequencies

GnomAD3 genomes

AF:

0.0265

AC:

4037

AN:

152246

Hom.:

167

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0920

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00890

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000470

Gnomad OTH

AF:

0.0234

GnomAD2 exomes

AF:

0.00728

AC:

1781

AN:

244676

AF XY:

0.00525

show subpopulations

Gnomad AFR exome

AF:

0.0974

Gnomad AMR exome

AF:

0.00620

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000372

Gnomad OTH exome

AF:

0.00348

GnomAD4 exome

AF:

0.00363

AC:

1376

AN:

379410

Hom.:

Cov.:

AF XY:

0.00264

AC XY:

570

AN XY:

216292

show subpopulations

African (AFR)

AF:

0.0934

AC:

978

AN:

10474

American (AMR)

AF:

0.00598

AC:

217

AN:

36302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11744

East Asian (EAS)

AF:

0.00

AC:

AN:

13174

South Asian (SAS)

AF:

0.000330

AC:

AN:

66684

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30746

Middle Eastern (MID)

AF:

0.00302

AC:

AN:

1654

European-Non Finnish (NFE)

AF:

0.000349

AC:

AN:

192042

Other (OTH)

AF:

0.00524

AC:

AN:

16590

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

164

245

327

409

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0266

AC:

4059

AN:

152364

Hom.:

171

Cov.:

AF XY:

0.0260

AC XY:

1937

AN XY:

74520

show subpopulations

African (AFR)

AF:

0.0923

AC:

3838

AN:

41580

American (AMR)

AF:

0.00888

AC:

136

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.000621

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000470

AC:

AN:

68034

Other (OTH)

AF:

0.0232

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

192

384

575

767

959

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

160

200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00582

Hom.:

Bravo

AF:

0.0308

Asia WGS

AF:

0.00491

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

7.1

(source)

DANN

Benign

0.85

PhyloP100

0.31

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over