rs730880268
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_173477.5(USH1G):c.186_187del(p.Ile63LeufsTer71) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,342 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
USH1G
NM_173477.5 frameshift
NM_173477.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.97
Genes affected
USH1G (HGNC:16356): (USH1 protein network component sans) This gene encodes a protein that contains three ankyrin domains, a class I PDZ-binding motif and a sterile alpha motif. The encoded protein interacts with harmonin, which is associated with Usher syndrome type 1C. This protein plays a role in the development and maintenance of the auditory and visual systems and functions in the cohesion of hair bundles formed by inner ear sensory cells. Mutations in this gene are associated with Usher syndrome type 1G (USH1G). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. There are 39 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 17-74920648-ATG-A is Pathogenic according to our data. Variant chr17-74920648-ATG-A is described in ClinVar as [Pathogenic]. Clinvar id is 2915.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-74920648-ATG-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
USH1G | NM_173477.5 | c.186_187del | p.Ile63LeufsTer71 | frameshift_variant | 2/3 | ENST00000614341.5 | |
USH1G | XM_011524296.2 | c.-124_-123del | 5_prime_UTR_variant | 2/3 | |||
USH1G | NM_001282489.3 | c.-92-32_-92-31del | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
USH1G | ENST00000614341.5 | c.186_187del | p.Ile63LeufsTer71 | frameshift_variant | 2/3 | 1 | NM_173477.5 | P1 | |
USH1G | ENST00000579243.1 | c.165-32_165-31del | intron_variant, NMD_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461342Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 726978
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GnomAD4 genome ? Cov.: 32
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Bravo
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Usher syndrome type 1G Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Mar 01, 2003 | - - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at