11-17509629-A-C

Variant names:

• chr11-17509629-A-C
• NM_153676.4:c.1740T>G
• USH1C p.Pro580Pro

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_153676.4(USH1C):​c.1740T>G​(p.Pro580Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P580P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 13)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: USH1C NM_153676.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.674
• Publications: 0 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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
• 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP7: Synonymous conserved (PhyloP=-0.674 with no splicing effect.

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.1740T>G	p.Pro580Pro	synonymous	Exon 18 of 27	NP_710142.1	Q9Y6N9-5
	USH1C	NM_005709.4	MANE Plus Clinical	c.1285-7649T>G		intron	N/A	NP_005700.2	A0A0S2Z4U9
	USH1C	NM_001440679.1		c.1470+2273T>G		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.1740T>G	p.Pro580Pro	synonymous	Exon 18 of 27	ENSP00000005226.7	Q9Y6N9-5
	USH1C	ENST00000318024.9	TSL:1 MANE Plus Clinical	c.1285-7649T>G		intron	N/A	ENSP00000317018.4	Q9Y6N9-1
	USH1C	ENST00000527020.5	TSL:1	c.1228-7649T>G		intron	N/A	ENSP00000436934.1	Q9Y6N9-4

Frequencies

GnomAD3 genomes Cov.: 13

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1170912 Hom.: 0 Cov.: 40 AF XY: 0.00 AC XY: 0 AN XY: 576850

African (AFR) AF: 0.00 AC: 0 AN: 26386

American (AMR) AF: 0.00 AC: 0 AN: 30966

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16456

East Asian (EAS) AF: 0.00 AC: 0 AN: 19856

South Asian (SAS) AF: 0.00 AC: 0 AN: 66492

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24120

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4324

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 939072

Other (OTH) AF: 0.00 AC: 0 AN: 43240

GnomAD4 genome Cov.: 13

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.39
PhyloP100		-0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr11-17531176;