X-149482521-TAA-T

Variant names:

• chrX-149482521-TAA-T
• rs71753099
• NM_000202.8:c.*223_*224delTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_000202.8(IDS):​c.*223_*224delTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000116 in 413,170 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 9 hemizygotes in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., 3 hem., cov: 7)
  • Exomes 𝑓: 0.00011 (0 hom. 6 hem.)
• Consequence: IDS NM_000202.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33

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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00013 (14/107567) while in subpopulation NFE AF= 0.000212 (11/51836). AF 95% confidence interval is 0.000118. There are 0 homozygotes in gnomad4. There are 3 alleles in male gnomad4 subpopulation. Median coverage is 7. This position pass quality control queck.
• BS2: High Hemizygotes in GnomAd4 at 3 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IDS	NM_000202.8	c.*223_*224delTT		3_prime_UTR_variant	Exon 9 of 9	ENST00000340855.11	NP_000193.1
IDS	NM_001166550.4	c.*223_*224delTT		3_prime_UTR_variant	Exon 9 of 9		NP_001160022.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IDS	ENST00000340855	c.*223_*224delTT		3_prime_UTR_variant	Exon 9 of 9	1	NM_000202.8	ENSP00000339801.6
ENSG00000241489	ENST00000651111	c.*223_*224delTT		3_prime_UTR_variant	Exon 14 of 14			ENSP00000498395.1
ENSG00000241489	ENST00000422081.6	c.*223_*224delTT		downstream_gene_variant		2		ENSP00000477056.1

Frequencies

GnomAD3 genomes AF: 0.000130 AC: 14 AN: 107567 Hom.: 0 Cov.: 7 AF XY: 0.0000982 AC XY: 3 AN XY: 30563

Gnomad AFR AF: 0.000102

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000212

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000111 AC: 34 AN: 305603 Hom.: 0 AF XY: 0.0000679 AC XY: 6 AN XY: 88301

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.000118

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000156

Gnomad4 OTH exome AF: 0.000113

GnomAD4 genome AF: 0.000130 AC: 14 AN: 107567 Hom.: 0 Cov.: 7 AF XY: 0.0000982 AC XY: 3 AN XY: 30563

Gnomad4 AFR AF: 0.000102

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000212

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

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;