Variant chr7-66286519-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The ENST00000304842.6(TPST1):c.854G>A(p.Arg285Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000591 in 1,590,870 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000059 ( 4 hom. )

Consequence

TPST1
ENST00000304842.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.84

Variant links:

Genes affected

TPST1 (HGNC:12020): (tyrosylprotein sulfotransferase 1) Enables protein homodimerization activity and protein-tyrosine sulfotransferase activity. Involved in peptidyl-tyrosine sulfation. Is integral component of Golgi membrane. [provided by Alliance of Genome Resources, Apr 2022]

TPST1 links:

TPST1 (HGNC:):

TPST1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07682896).

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPST1	NM_003596.4 linkuse as main transcript	c.854G>A	p.Arg285Lys	missense_variant	3/6	ENST00000304842.6	NP_003587.1	O60507A0A024RDK9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TPST1	ENST00000304842.6 linkuse as main transcript	c.854G>A	p.Arg285Lys	missense_variant	3/6	1	NM_003596.4	ENSP00000302413.5	O60507
TPST1	ENST00000480281.5 linkuse as main transcript	n.198G>A		non_coding_transcript_exon_variant	2/5	1
TPST1	ENST00000649664.1 linkuse as main transcript	c.854G>A	p.Arg285Lys	missense_variant	4/7			ENSP00000497281.1	O60507

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

152086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000963

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.0000628

AC:

AN:

238778

Hom.:

AF XY:

0.0000309

AC XY:

AN XY:

129554

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000830

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000176

GnomAD4 exome

AF:

0.0000591

AC:

AN:

1438666

Hom.:

Cov.:

AF XY:

0.0000545

AC XY:

AN XY:

715700

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000366

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.10e-7

Gnomad4 OTH exome

AF:

0.00118

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000965

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00142

Bravo

AF:

0.0000718

ExAC

AF:

0.0000577

AC:

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 28, 2023

The c.854G>A (p.R285K) alteration is located in exon 3 (coding exon 2) of the TPST1 gene. This alteration results from a G to A substitution at nucleotide position 854, causing the arginine (R) at amino acid position 285 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.46

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.30

T;T

Eigen

Benign

0.13

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.95

.;D

M_CAP

Benign

0.0081

MetaRNN

Benign

0.077

T;T

MetaSVM

Benign

-0.85

MutationAssessor

Benign

1.3

L;L

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-2.0

N;.

REVEL

Benign

0.087

Sift

Benign

0.21

T;.

Sift4G

Benign

0.45

T;.

Polyphen

0.036

B;B

Vest4

0.41

MutPred

0.41

Gain of ubiquitination at R285 (P = 0.0146);Gain of ubiquitination at R285 (P = 0.0146);

MVP

0.39

MPC

0.30

ClinPred

0.12

GERP RS

5.7

Varity_R

0.56

gMVP

0.69

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over