11-17527112-ACCTGCTCCCCCGCCCTCCCTCCCTCCCACCGTCATGGAGTACTGC-A

Position:

• chr11-17527112-ACCTGCTCCCCCGCCCTCCCTCCCTCCCACCGTCATGGAGTACTGC-A

Variant summary

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

The NM_153676.4(USH1C):​c.496+66_497-73del variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.47 (3670 hom., cov: 0)
  • Exomes 𝑓: 0.23 (35864 hom.)
  • Failed GnomAD Quality Control
• Consequence: USH1C NM_153676.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.428

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 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USH1C	NM_005709.4	c.496+66_497-73del		intron_variant		ENST00000318024.9	NP_005700.2
USH1C	NM_153676.4	c.496+66_497-73del		intron_variant		ENST00000005226.12	NP_710142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USH1C	ENST00000005226.12	c.496+66_497-73del		intron_variant		5	NM_153676.4	ENSP00000005226
USH1C	ENST00000318024.9	c.496+66_497-73del		intron_variant		1	NM_005709.4	ENSP00000317018	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 29683 AN: 63770 Hom.: 3664 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.424

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.515

Gnomad EAS AF: 0.489

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.509

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.459

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.235 AC: 188239 AN: 802520 Hom.: 35864 AF XY: 0.248 AC XY: 98461 AN XY: 397634

Gnomad4 AFR exome AF: 0.266

Gnomad4 AMR exome AF: 0.366

Gnomad4 ASJ exome AF: 0.408

Gnomad4 EAS exome AF: 0.558

Gnomad4 SAS exome AF: 0.326

Gnomad4 FIN exome AF: 0.482

Gnomad4 NFE exome AF: 0.184

Gnomad4 OTH exome AF: 0.305

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.465 AC: 29698 AN: 63814 Hom.: 3670 Cov.: 0 AF XY: 0.457 AC XY: 13498 AN XY: 29518

Gnomad4 AFR AF: 0.424

Gnomad4 AMR AF: 0.445

Gnomad4 ASJ AF: 0.515

Gnomad4 EAS AF: 0.490

Gnomad4 SAS AF: 0.398

Gnomad4 FIN AF: 0.509

Gnomad4 NFE AF: 0.486

Gnomad4 OTH AF: 0.456

ClinVar

Not reported in ClinVar

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;