11-17527112-ACCTGCTCCCCCGCCCTCCCTCCCTCCCACCGTCATGGAGTACTGCCCTGCTCCCCCGCCCTCCCTCCCTCCCACCGTCATGGAGTACTGC-ACCTGCTCCCCCGCCCTCCCTCCCTCCCACCGTCATGGAGTACTGC

Variant names:

• chr11-17527112-ACCTGCTCCCCCGCCCTCCCTCCCTCCCACCGTCATGGAGTACTGC-A
• rs55983148
• NM_153676.4:c.496+66_497-73delGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGG

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_153676.4(USH1C):​c.496+66_497-73delGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGG variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. 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
• Publications: 3 publications found

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]

USH1C Gene-Disease associations (from GenCC):

• Usher syndrome type 1C

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Laboratory for Molecular Medicine, G2P
• Usher syndrome type 1

  Inheritance: Unknown, AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• autosomal recessive nonsyndromic hearing loss 18A

  Inheritance: AR, Unknown Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153676.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USH1C	NM_153676.4	MANE Select	c.496+66_497-73delGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGG		intron	N/A	NP_710142.1	Q9Y6N9-5
	USH1C	NM_005709.4	MANE Plus Clinical	c.496+66_497-73delGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGG		intron	N/A	NP_005700.2	A0A0S2Z4U9
	USH1C	NM_001440679.1		c.529+66_530-73delGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGG		intron	N/A	NP_001427608.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USH1C	ENST00000005226.12	TSL:5 MANE Select	c.496+66_497-73delGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGG		intron	N/A	ENSP00000005226.7	Q9Y6N9-5
	USH1C	ENST00000318024.9	TSL:1 MANE Plus Clinical	c.496+66_497-73delGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGG		intron	N/A	ENSP00000317018.4	Q9Y6N9-1
	USH1C	ENST00000527020.5	TSL:1	c.496+66_497-73delGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGG		intron	N/A	ENSP00000436934.1	Q9Y6N9-4

Frequencies

GnomAD3 genomes AF: 0.465 AC: 29683 AN: 63770 Hom.: 3664 Cov.: 0

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

African (AFR) AF: 0.266 AC: 4904 AN: 18404

American (AMR) AF: 0.366 AC: 8609 AN: 23542

Ashkenazi Jewish (ASJ) AF: 0.408 AC: 6854 AN: 16788

East Asian (EAS) AF: 0.558 AC: 15872 AN: 28422

South Asian (SAS) AF: 0.326 AC: 16119 AN: 49370

European-Finnish (FIN) AF: 0.482 AC: 14243 AN: 29576

Middle Eastern (MID) AF: 0.344 AC: 913 AN: 2656

European-Non Finnish (NFE) AF: 0.184 AC: 110242 AN: 599362

Other (OTH) AF: 0.305 AC: 10483 AN: 34400

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

African (AFR) AF: 0.424 AC: 7072 AN: 16696

American (AMR) AF: 0.445 AC: 2743 AN: 6168

Ashkenazi Jewish (ASJ) AF: 0.515 AC: 981 AN: 1904

East Asian (EAS) AF: 0.490 AC: 1164 AN: 2376

South Asian (SAS) AF: 0.398 AC: 591 AN: 1486

European-Finnish (FIN) AF: 0.509 AC: 1773 AN: 3484

Middle Eastern (MID) AF: 0.448 AC: 52 AN: 116

European-Non Finnish (NFE) AF: 0.486 AC: 14780 AN: 30428

Other (OTH) AF: 0.456 AC: 370 AN: 812

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.43

Splicing

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

Other links and lift over

dbSNP: rs55983148; hg19: chr11-17548659;