chrX-149487080-T-G
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PM2PP3_StrongPP5_Very_Strong
The NM_000202.8(IDS):c.1025A>C(p.His342Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★).
Frequency
Consequence
NM_000202.8 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 14 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
IDS | ENST00000340855.11 | c.1025A>C | p.His342Pro | missense_variant | Exon 8 of 9 | 1 | NM_000202.8 | ENSP00000339801.6 | ||
ENSG00000241489 | ENST00000651111.1 | c.392A>C | p.His131Pro | missense_variant | Exon 13 of 14 | ENSP00000498395.1 | ||||
ENSG00000241489 | ENST00000422081.6 | c.392A>C | p.His131Pro | missense_variant | Exon 8 of 9 | 2 | ENSP00000477056.1 | |||
ENSG00000241489 | ENST00000441880.1 | n.132A>C | non_coding_transcript_exon_variant | Exon 2 of 3 | 2 |
Frequencies
GnomAD3 genomes Cov.: 22
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 22
ClinVar
Submissions by phenotype
Mucopolysaccharidosis, MPS-II Pathogenic:2
Likely pathogenic variation identified in a Hunter syndrome male patient without I2S evaluation. He presents mental retardation, but no seizures, nor hydrocephaly. Pathogenicity clues: Highly conserved nucleotide (phyloP: 0.96 [-5.2;1.1]); Highly conserved amino acid, up to Fruitfly (considering 12 species); Moderate physicochemical difference between His and Pro (Grantham dist.: 77 [0-215]); This variant is in protein domains: Sulfatase, Alkaline-phosphatase-like, core domain, Align GVGD: C0 (GV: 353.86 - GD: 0.00); SIFT: Deleterious (score: 0, median: 3.50); MutationTaster: disease causing (p-value: 1); PolyPhen prediction: Probably Damaging (score 1.0) -
Prevalence of the variant significantly increased in affected individuals compared with controls (PS4_Supporting), Absent from controls (or at low frequency) in gnomAD database (PM2_Moderate), Missense variant in a gene with a low rate of benign missense variation (PP2_Supporting), Multiple lines of computational evidence support a deleterious effect (PP3_Supporting), Patient’s phenotype or family history highly specific for the disease (PP4_Strong) -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at