rs1557338131

chrX-149487006-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_000202.8(IDS):c.1099A>T(p.Thr367Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T367M) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 23)
• Consequence: IDS NM_000202.8 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.27

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant X-149487006-T-A is Benign according to our data. Variant chrX-149487006-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 437444.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IDS	NM_000202.8	c.1099A>T	p.Thr367Ser	missense_variant	8/9	ENST00000340855.11
IDS	NM_001166550.4	c.829A>T	p.Thr277Ser	missense_variant	8/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IDS	ENST00000340855.11	c.1099A>T	p.Thr367Ser	missense_variant	8/9	1	NM_000202.8	P1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Mucopolysaccharidosis, MPS-II Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genomic Research Center, Shahid Beheshti University of Medical Sciences

Nov 06, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.070
Cadd	Benign	23
Dann	Benign	0.94
DEOGEN2	Pathogenic	0.85	D;.
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.47	T;T
M_CAP	Pathogenic	0.76	D
MetaRNN	Uncertain	0.54	D;D
MetaSVM	Pathogenic	0.90	D
MutationAssessor	Benign	1.1	L;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-2.6	D;.
REVEL	Uncertain	0.64
Sift	Benign	0.20	T;.
Sift4G	Benign	0.25	T;T
Polyphen		0.62	P;.
Vest4		0.41
MutPred		0.45		Gain of disorder (P = 0.0446);.;
MVP		0.93
MPC		0.50
ClinPred		0.89	D
GERP RS		5.3
Varity_R		0.72
gMVP		0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs1557338131; hg19: chrX-148568537;