17-74916891-G-GCA
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BS1_Supporting
The NM_173477.5(USH1G):c.*1180_*1181dupTG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000302 in 152,410 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0073 ( 0 hom. )
Consequence
USH1G
NM_173477.5 3_prime_UTR
NM_173477.5 3_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.909
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 Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000264 (40/151588) while in subpopulation AMR AF= 0.00158 (24/15226). AF 95% confidence interval is 0.00109. There are 0 homozygotes in gnomad4. There are 15 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| USH1G | NM_173477.5 | c.*1180_*1181dupTG | 3_prime_UTR_variant | 3/3 | ENST00000614341.5 | NP_775748.2 | ||
| USH1G | NM_001282489.3 | c.*1180_*1181dupTG | 3_prime_UTR_variant | 3/3 | NP_001269418.1 | |||
| USH1G | XM_011524296.2 | c.*1180_*1181dupTG | 3_prime_UTR_variant | 3/3 | XP_011522598.1 |
Ensembl
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GnomAD3 genomes 0.000264 AC: 40AN: 151470Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 0.00730 AC: 6AN: 822Hom.: 0 Cov.: 0 AF XY: 0.00839 AC XY: 5AN XY: 596
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GnomAD4 genome 0.000264 AC: 40AN: 151588Hom.: 0 Cov.: 33 AF XY: 0.000203 AC XY: 15AN XY: 74064
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Retinitis pigmentosa-deafness syndrome Uncertain:1
| Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at