X-149482521-T-TA

Position:

• chrX-149482521-T-TA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_000202.8(IDS):​c.*224dupT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0058 (7 hom., 160 hem., cov: 7)
  • Exomes 𝑓: 0.0085 (1 hom. 22 hem.)
• Consequence: IDS NM_000202.8 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.135

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]

ENSG00000241489 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant X-149482521-T-TA is Benign according to our data. Variant chrX-149482521-T-TA is described in ClinVar as [Likely_benign]. Clinvar id is 1198719.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00585 (629/107570) while in subpopulation AFR AF= 0.0197 (583/29579). AF 95% confidence interval is 0.0184. There are 7 homozygotes in gnomad4. There are 160 alleles in male gnomad4 subpopulation. Median coverage is 7. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 7 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IDS	NM_000202.8	c.*224dupT		3_prime_UTR_variant	9/9	ENST00000340855.11	NP_000193.1
IDS	NM_001166550.4	c.*224dupT		3_prime_UTR_variant	9/9		NP_001160022.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IDS	ENST00000340855	c.*224dupT		3_prime_UTR_variant	9/9	1	NM_000202.8	ENSP00000339801.6
ENSG00000241489	ENST00000651111	c.*224dupT		3_prime_UTR_variant	14/14			ENSP00000498395.1
ENSG00000241489	ENST00000422081.6	c.*224dupT		downstream_gene_variant		2		ENSP00000477056.1

Frequencies

GnomAD3 genomes AF: 0.00577 AC: 621 AN: 107536 Hom.: 7 Cov.: 7 AF XY: 0.00501 AC XY: 153 AN XY: 30538

Gnomad AFR AF: 0.0195

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00219

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000580

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00444

Gnomad NFE AF: 0.000386

Gnomad OTH AF: 0.000694

GnomAD4 exome AF: 0.00854 AC: 2477 AN: 290133 Hom.: 1 Cov.: 0 AF XY: 0.000276 AC XY: 22 AN XY: 79779

Gnomad4 AFR exome AF: 0.0275

Gnomad4 AMR exome AF: 0.0144

Gnomad4 ASJ exome AF: 0.00977

Gnomad4 EAS exome AF: 0.0162

Gnomad4 SAS exome AF: 0.00595

Gnomad4 FIN exome AF: 0.00608

Gnomad4 NFE exome AF: 0.00697

Gnomad4 OTH exome AF: 0.0105

GnomAD4 genome AF: 0.00585 AC: 629 AN: 107570 Hom.: 7 Cov.: 7 AF XY: 0.00523 AC XY: 160 AN XY: 30584

Gnomad4 AFR AF: 0.0197

Gnomad4 AMR AF: 0.00218

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000582

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000386

Gnomad4 OTH AF: 0.000685

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 13, 2019

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs71753099; hg19: chrX-148564052;