11-17527112-ACCTGCTCCCCCGCCCTCCCTCCCTCCCACCGTCATGGAGTACTGC-ACCTGCTCCCCCGCCCTCCCTCCCTCCCACCGTCATGGAGTACTGCCCTGCTCCCCCGCCCTCCCTCCCTCCCACCGTCATGGAGTACTGCCCTGCTCCCCCGCCCTCCCTCCCTCCCACCGTCATGGAGTACTGCCCTGCTCCCCCGCCCTCCCTCCCTCCCACCGTCATGGAGTACTGCCCTGCTCCCCCGCCCTCCCTCCCTCCCACCGTCATGGAGTACTGCCCTGCTCCCCCGCCCTCCCTCCCTCCCACCGTCATGGAGTACTGCCCTGCTCCCCCGCCCTCCCTCCCTCCCACCGTCATGGAGTACTGCCCTGCTCCCCCGCCCTCCCTCCCTCCCACCGTCATGGAGTACTGC

Position:

• chr11-17527112-ACCTGCTCCCCCGCCCTCCCTCCCTCCCACCGTCATGGAGTACTGC-ACCTGCTCCCCCGCCCTCCCTCCCTCCCACCGTCATGGAGTACTGCCCTGCTCCCCCGCCCTCCCTCCCTCCCACCGTCATGGAGTACTGCCCTGCTCCCCCGCCCTCCCTCCCTCCCACCGTCATGGAGTACTGCCCTGCTCCCCCGCCCTCCCTCCCTCCCACCGTCATGGAGTACTGCCCTGCTCCCCCGCCCTCCCTCCCTCCCACCGTCATGGAGTACTGCCCTGCTCCCCCGCCCTCCCTCCCTCCCACCGTCATGGAGTACTGCCCTGCTCCCCCGCCCTCCCTCCCTCCCACCGTCATGGAGTACTGCCCTGCTCCCCCGCCCTCCCTCCCTCCCACCGTCATGGAGTACTGC

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

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
• Clinical Significance: Pathogenic no assertion criteria provided P:1 O:2
• Conservation: PhyloP100: 0.370

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]

ACMG classification

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
USH1C	NM_153676.4	c.497-73_497-72insGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGGGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGGGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGGGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGGGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGGGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGGGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGG		intron_variant		ENST00000005226.12	NP_710142.1
USH1C	NM_005709.4	c.497-73_497-72insGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGGGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGGGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGGGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGGGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGGGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGGGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGG		intron_variant		ENST00000318024.9	NP_005700.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USH1C	ENST00000005226.12	c.497-73_497-72insGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGGGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGGGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGGGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGGGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGGGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGGGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGG		intron_variant		5	NM_153676.4	ENSP00000005226.7
USH1C	ENST00000318024.9	c.497-73_497-72insGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGGGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGGGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGGGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGGGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGGGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGGGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGG		intron_variant		1	NM_005709.4	ENSP00000317018.4

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Cov.: 23

GnomAD4 genome Cov.: 0

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1 Other:2

Revision: no assertion criteria provided

Submissions by phenotype

Usher syndrome type 1C Pathogenic:1 Other:1

not provided, no classification provided	literature only	GeneReviews	-	- -
Pathogenic, no assertion criteria provided	literature only	OMIM	Jan 01, 2002	- -

Usher syndrome type 1 Other:1

not provided, no classification provided

literature only

GeneReviews

-

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs55983148; hg19: chr11-17548659;