Variant chr1-87092574-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3_ModeratePP5

The NM_012262.4(HS2ST1):c.493G>T(p.Asp165Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000119 in 1,431,010 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

HS2ST1
NM_012262.4 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 9.91

Variant links:

Genes affected

HS2ST1 (HGNC:5193): (heparan sulfate 2-O-sulfotransferase 1) Heparan sulfate biosynthetic enzymes are key components in generating a myriad of distinct heparan sulfate fine structures that carry out multiple biologic activities. This gene encodes a member of the heparan sulfate biosynthetic enzyme family that transfers sulfate to the 2 position of the iduronic acid residue of heparan sulfate. The disruption of this gene resulted in no kidney formation in knockout embryonic mice, indicating that the absence of this enzyme may interfere with the signaling required for kidney formation. Two alternatively spliced transcript variants that encode different proteins have been found for this gene. [provided by RefSeq, Aug 2008]

HS2ST1 links:

ENSG00000267561 (HGNC:):

ENSG00000267561 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.863

PP5

Variant 1-87092574-G-T is Pathogenic according to our data. Variant chr1-87092574-G-T is described in ClinVar as [Pathogenic]. Clinvar id is 997412.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HS2ST1	NM_012262.4 linkuse as main transcript	c.493G>T	p.Asp165Tyr	missense_variant	4/7	ENST00000370550.10	NP_036394.1	Q7LGA3-1
HS2ST1	NM_001134492.2 linkuse as main transcript	c.493G>T	p.Asp165Tyr	missense_variant	4/5		NP_001127964.1	Q7LGA3-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HS2ST1	ENST00000370550.10 linkuse as main transcript	c.493G>T	p.Asp165Tyr	missense_variant	4/7	1	NM_012262.4	ENSP00000359581.4		Q7LGA3-1
ENSG00000267561	ENST00000370548.3 linkuse as main transcript	c.415G>T	p.Asp139Tyr	missense_variant	4/8	2		ENSP00000359579.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000869

AC:

AN:

230026

Hom.:

AF XY:

0.0000160

AC XY:

AN XY:

125040

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:

0.0000188

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000119

AC:

AN:

1431010

Hom.:

Cov.:

AF XY:

0.0000140

AC XY:

AN XY:

712270

show subpopulations

Gnomad4 AFR exome

AF:

0.0000316

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:

0.0000137

Gnomad4 OTH exome

AF:

0.0000169

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Neurofacioskeletal syndrome with or without renal agenesis

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Feb 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.84

BayesDel_addAF

Pathogenic

0.45

BayesDel_noAF

Pathogenic

0.43

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.92

.;D;D;.

Eigen

Pathogenic

0.96

Eigen_PC

Pathogenic

0.93

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.97

D;D;D;D

M_CAP

Benign

0.078

MetaRNN

Pathogenic

0.86

D;D;D;D

MetaSVM

Uncertain

0.66

MutationAssessor

Pathogenic

3.1

M;M;.;.

PrimateAI

Pathogenic

0.89

PROVEAN

Uncertain

-2.8

D;D;.;D

REVEL

Pathogenic

0.84

Sift

Uncertain

0.012

D;D;.;D

Sift4G

Uncertain

0.0070

D;D;D;D

Polyphen

1.0

.;D;.;.

Vest4

0.97

MutPred

0.73

Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);.;.;

MVP

0.91

MPC

1.4, 1.1

ClinPred

0.94

GERP RS

5.5

Varity_R

0.49

gMVP

0.98

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.22

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.22

Position offset: -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