dbSNP rs3752523: TPST2:c.1041+104C>T (chr22-26536184-G-A) – 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.1041+104C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 1,345,114 control chromosomes in the GnomAD database, including 193,073 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 0.47 ( 17968 hom., cov: 32)

Exomes 𝑓: 0.54 ( 175105 hom. )

Consequence

TPST2
NM_003595.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.473

Publications

11 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=4.069336E-5).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.552 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TPST2	NM_003595.5	MANE Select	c.1041+104C>T	intron	N/A	NP_003586.3
TPST2	NM_001362923.2		c.1203+104C>T	intron	N/A	NP_001349852.1
TPST2	NM_001008566.3		c.1041+104C>T	intron	N/A	NP_001008566.1	O60704

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TPST2	ENST00000338754.9	TSL:1 MANE Select	c.1041+104C>T		intron	N/A	ENSP00000339813.4	O60704
TPST2	ENST00000445720.1	TSL:2	c.386C>T	p.Pro129Leu	missense	Exon 2 of 2	ENSP00000403758.1	B1AHJ5
TPST2	ENST00000910417.1		c.1059+104C>T		intron	N/A	ENSP00000580476.1

Frequencies

GnomAD3 genomes

AF:

0.473

AC:

71872

AN:

151824

Hom.:

17966

Cov.:

show subpopulations

Gnomad AFR

AF:

0.338

Gnomad AMI

AF:

0.602

Gnomad AMR

AF:

0.417

Gnomad ASJ

AF:

0.543

Gnomad EAS

AF:

0.367

Gnomad SAS

AF:

0.391

Gnomad FIN

AF:

0.603

Gnomad MID

AF:

0.465

Gnomad NFE

AF:

0.556

Gnomad OTH

AF:

0.479

GnomAD2 exomes

AF:

0.481

AC:

79819

AN:

165872

AF XY:

0.484

show subpopulations

Gnomad AFR exome

AF:

0.336

Gnomad AMR exome

AF:

0.356

Gnomad ASJ exome

AF:

0.537

Gnomad EAS exome

AF:

0.390

Gnomad FIN exome

AF:

0.591

Gnomad NFE exome

AF:

0.552

Gnomad OTH exome

AF:

0.515

GnomAD4 exome

AF:

0.536

AC:

639748

AN:

1193172

Hom.:

175105

Cov.:

AF XY:

0.533

AC XY:

319749

AN XY:

599356

show subpopulations

African (AFR)

AF:

0.339

AC:

9281

AN:

27364

American (AMR)

AF:

0.363

AC:

12955

AN:

35728

Ashkenazi Jewish (ASJ)

AF:

0.539

AC:

12864

AN:

23876

East Asian (EAS)

AF:

0.352

AC:

12308

AN:

35008

South Asian (SAS)

AF:

0.417

AC:

31269

AN:

74970

European-Finnish (FIN)

AF:

0.593

AC:

29632

AN:

49952

Middle Eastern (MID)

AF:

0.457

AC:

2438

AN:

5334

European-Non Finnish (NFE)

AF:

0.565

AC:

502240

AN:

889668

Other (OTH)

AF:

0.522

AC:

26761

AN:

51272

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

13623

27246

40869

54492

68115

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12954

25908

38862

51816

64770

<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:

0.473

AC:

71887

AN:

151942

Hom.:

17968

Cov.:

AF XY:

0.472

AC XY:

35053

AN XY:

74274

show subpopulations

African (AFR)

AF:

0.338

AC:

14003

AN:

41418

American (AMR)

AF:

0.416

AC:

6357

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.543

AC:

1880

AN:

3464

East Asian (EAS)

AF:

0.368

AC:

1894

AN:

5148

South Asian (SAS)

AF:

0.392

AC:

1887

AN:

4818

European-Finnish (FIN)

AF:

0.603

AC:

6363

AN:

10544

Middle Eastern (MID)

AF:

0.452

AC:

132

AN:

292

European-Non Finnish (NFE)

AF:

0.556

AC:

37821

AN:

67964

Other (OTH)

AF:

0.475

AC:

1002

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1856

3712

5568

7424

9280

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

654

1308

1962

2616

3270

<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:

0.517

Hom.:

37396

Bravo

AF:

0.455

TwinsUK

AF:

0.551

AC:

2043

ALSPAC

AF:

0.556

AC:

2142

ExAC

AF:

0.402

AC:

44226

Asia WGS

AF:

0.342

AC:

1189

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.57

CADD

Benign

3.9

(source)

DANN

Uncertain

0.98

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.065

LIST_S2

Benign

0.32

MetaRNN

Benign

0.000041

MetaSVM

Benign

-0.94

PhyloP100

0.47

PROVEAN

Benign

-1.1

REVEL

Benign

0.0080

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

ClinPred

0.0088

GERP RS

-0.28

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over