Variant chrX-149496444-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The NM_000202.8(IDS):c.781C>A(p.Pro261Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000164 in 1,095,325 control chromosomes in the GnomAD database, including 1 homozygotes. There are 5 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.000016 ( 1 hom. 5 hem. )

Consequence

IDS
NM_000202.8 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0170

Variant links:

Genes affected

IDS (HGNC:5389): (iduronate 2-sulfatase) This gene encodes a member of the sulfatase family of proteins. The encoded preproprotein is proteolytically processed to generate two polypeptide chains. This enzyme is involved in the lysosomal degradation of heparan sulfate and dermatan sulfate. Mutations in this gene are associated with the X-linked lysosomal storage disease mucopolysaccharidosis type II, also known as Hunter syndrome. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed. [provided by RefSeq, Jan 2016]

IDS links:

ENSG00000241489 (HGNC:):

ENSG00000241489 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2224598).

BP6

Variant X-149496444-G-T is Benign according to our data. Variant chrX-149496444-G-T is described in ClinVar as [Benign]. Clinvar id is 1170676.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.0000164 (18/1095325) while in subpopulation SAS AF= 0.000222 (12/54071). AF 95% confidence interval is 0.000128. There are 1 homozygotes in gnomad4_exome. There are 5 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Hemizygotes in GnomAdExome4 at 5 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IDS	NM_000202.8 link	c.781C>A	p.Pro261Thr	missense_variant	6/9	ENST00000340855.11	NP_000193.1	P22304-1
IDS	NM_001166550.4 link	c.511C>A	p.Pro171Thr	missense_variant	6/9		NP_001160022.1	P22304B4DGD7
IDS	NM_006123.5 link	c.781C>A	p.Pro261Thr	missense_variant	6/8		NP_006114.1	P22304-2
IDS	NR_104128.2 link	n.950C>A		non_coding_transcript_exon_variant	6/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IDS	ENST00000340855.11 link	c.781C>A	p.Pro261Thr	missense_variant	6/9	1	NM_000202.8	ENSP00000339801.6		P22304-1
ENSG00000241489	ENST00000651111.1 link	c.148C>A	p.Pro50Thr	missense_variant	11/14			ENSP00000498395.1		B3KWA1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000601

AC:

AN:

183076

Hom.:

AF XY:

0.0000444

AC XY:

AN XY:

67618

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:

0.000577

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000164

AC:

AN:

1095325

Hom.:

Cov.:

AF XY:

0.0000139

AC XY:

AN XY:

360805

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:

0.000222

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000238

Gnomad4 OTH exome

AF:

0.0000870

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000824

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Mucopolysaccharidosis, MPS-II

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 16, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.14

CADD

Benign

9.4

DANN

Benign

0.82

DEOGEN2

Uncertain

0.78

D;.;.

FATHMM_MKL

Benign

0.23

LIST_S2

Uncertain

0.89

D;D;D

M_CAP

Pathogenic

0.78

MetaRNN

Benign

0.22

T;T;T

MetaSVM

Pathogenic

1.1

MutationAssessor

Benign

0.64

N;N;.

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.96

N;N;.

REVEL

Uncertain

0.41

Sift

Benign

0.97

T;T;.

Sift4G

Benign

0.78

T;T;T

Polyphen

0.0030

B;B;.

Vest4

0.22

MutPred

0.51

Loss of catalytic residue at P260 (P = 0.0121);Loss of catalytic residue at P260 (P = 0.0121);.;

MVP

0.79

MPC

0.23

ClinPred

0.051

GERP RS

2.8

Varity_R

0.25

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