11-17527112-ACCTGCTCCCCCGCCCTCCCTCCCTCCCACCGTCATGGAGTACTGC-ACCTGCTCCCCCGCCCTCCCTCCCTCCCACCGTCATGGAGTACTGCCCTGCTCCCCCGCCCTCCCTCCCTCCCACCGTCATGGAGTACTGCCCTGCTCCCCCGCCCTCCCTCCCTCCCACCGTCATGGAGTACTGCCCTGCTCCCCCGCCCTCCCTCCCTCCCACCGTCATGGAGTACTGCCCTGCTCCCCCGCCCTCCCTCCCTCCCACCGTCATGGAGTACTGCCCTGCTCCCCCGCCCTCCCTCCCTCCCACCGTCATGGAGTACTGCCCTGCTCCCCCGCCCTCCCTCCCTCCCACCGTCATGGAGTACTGCCCTGCTCCCCCGCCCTCCCTCCCTCCCACCGTCATGGAGTACTGC

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP5

The NM_153676.4(USH1C):​c.497-73_497-72insGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGGGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGGGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGGGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGGGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGGGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGGGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 0)

Consequence

USH1C
NM_153676.4 intron

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:1O:2

Conservation

PhyloP100: 0.370
Variant links:
Genes affected
USH1C (HGNC:12597): (USH1 protein network component harmonin) This gene encodes a scaffold protein that functions in the assembly of Usher protein complexes. The protein contains PDZ domains, a coiled-coil region with a bipartite nuclear localization signal and a PEST degradation sequence. Defects in this gene are the cause of Usher syndrome type 1C and non-syndromic sensorineural deafness autosomal recessive type 18. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 11-17527112-A-ACCTGCTCCCCCGCCCTCCCTCCCTCCCACCGTCATGGAGTACTGCCCTGCTCCCCCGCCCTCCCTCCCTCCCACCGTCATGGAGTACTGCCCTGCTCCCCCGCCCTCCCTCCCTCCCACCGTCATGGAGTACTGCCCTGCTCCCCCGCCCTCCCTCCCTCCCACCGTCATGGAGTACTGCCCTGCTCCCCCGCCCTCCCTCCCTCCCACCGTCATGGAGTACTGCCCTGCTCCCCCGCCCTCCCTCCCTCCCACCGTCATGGAGTACTGCCCTGCTCCCCCGCCCTCCCTCCCTCCCACCGTCATGGAGTACTGC is Pathogenic according to our data. Variant chr11-17527112-A-ACCTGCTCCCCCGCCCTCCCTCCCTCCCACCGTCATGGAGTACTGCCCTGCTCCCCCGCCCTCCCTCCCTCCCACCGTCATGGAGTACTGCCCTGCTCCCCCGCCCTCCCTCCCTCCCACCGTCATGGAGTACTGCCCTGCTCCCCCGCCCTCCCTCCCTCCCACCGTCATGGAGTACTGCCCTGCTCCCCCGCCCTCCCTCCCTCCCACCGTCATGGAGTACTGCCCTGCTCCCCCGCCCTCCCTCCCTCCCACCGTCATGGAGTACTGCCCTGCTCCCCCGCCCTCCCTCCCTCCCACCGTCATGGAGTACTGC is described in ClinVar as [Pathogenic]. Clinvar id is 5142.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
USH1CNM_153676.4 linkc.497-73_497-72insGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGGGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGGGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGGGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGGGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGGGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGGGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGG intron_variant ENST00000005226.12 NP_710142.1 Q9Y6N9-5
USH1CNM_005709.4 linkc.497-73_497-72insGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGGGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGGGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGGGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGGGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGGGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGGGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGG intron_variant ENST00000318024.9 NP_005700.2 Q9Y6N9-1A0A0S2Z4U9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
USH1CENST00000005226.12 linkc.497-73_497-72insGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGGGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGGGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGGGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGGGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGGGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGGGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGG intron_variant 5 NM_153676.4 ENSP00000005226.7 Q9Y6N9-5
USH1CENST00000318024.9 linkc.497-73_497-72insGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGGGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGGGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGGGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGGGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGGGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGGGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGG intron_variant 1 NM_005709.4 ENSP00000317018.4 Q9Y6N9-1

Frequencies

GnomAD3 genomes
Cov.:
0
GnomAD4 exome
Cov.:
23
GnomAD4 genome
Cov.:
0

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1Other:2
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Usher syndrome type 1C Pathogenic:1Other:1
Pathogenic, no assertion criteria providedliterature onlyOMIMJan 01, 2002- -
not provided, no classification providedliterature onlyGeneReviews-- -
Usher syndrome type 1 Other:1
not provided, no classification providedliterature onlyGeneReviews-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs55983148; hg19: chr11-17548659; API