Variant 7-66352539-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000304842.6(TPST1):c.1079T>C(p.Leu360Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,734 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TPST1
ENST00000304842.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.52

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPST1	NM_003596.4 linkuse as main transcript	c.1079T>C	p.Leu360Pro	missense_variant	4/6	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.1079T>C	p.Leu360Pro	missense_variant	4/6	1	NM_003596.4	ENSP00000302413.5	O60507
TPST1	ENST00000480281.5 linkuse as main transcript	n.423T>C		non_coding_transcript_exon_variant	3/5	1
TPST1	ENST00000649664.1 linkuse as main transcript	c.1079T>C	p.Leu360Pro	missense_variant	5/7			ENSP00000497281.1	O60507
TPST1	ENST00000490159.1 linkuse as main transcript	n.36T>C		non_coding_transcript_exon_variant	1/3	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000400

AC:

AN:

250160

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135310

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460734

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726712

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

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

Mar 01, 2024

The c.1079T>C (p.L360P) alteration is located in exon 4 (coding exon 3) of the TPST1 gene. This alteration results from a T to C substitution at nucleotide position 1079, causing the leucine (L) at amino acid position 360 to be replaced by a proline (P). 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

Pathogenic

0.83

BayesDel_addAF

Pathogenic

0.28

BayesDel_noAF

Pathogenic

0.17

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.51

D;D

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.81

.;T

M_CAP

Benign

0.029

MetaRNN

Uncertain

0.68

D;D

MetaSVM

Benign

-0.29

MutationAssessor

Uncertain

2.4

M;M

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.70

PROVEAN

Uncertain

-2.8

D;.

REVEL

Benign

0.24

Sift

Uncertain

0.0010

D;.

Sift4G

Uncertain

0.0020

D;.

Polyphen

0.72

P;P

Vest4

0.73

MutPred

0.49

Gain of relative solvent accessibility (P = 0.0082);Gain of relative solvent accessibility (P = 0.0082);

MVP

0.47

MPC

0.86

ClinPred

0.97

GERP RS

5.0

Varity_R

0.90

gMVP

0.92

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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