rs115931035

chr11-17517424-C-Achr11-17517424-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_005709.4(USH1C):c.1261G>T(p.Gly421Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G421S) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: USH1C NM_005709.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.14

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 Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.22759447).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USH1C	NM_005709.4	c.1261G>T	p.Gly421Cys	missense_variant	15/21	ENST00000318024.9
USH1C	NM_153676.4	c.1211-1134G>T		intron_variant		ENST00000005226.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USH1C	ENST00000318024.9	c.1261G>T	p.Gly421Cys	missense_variant	15/21	1	NM_005709.4	P1
USH1C	ENST00000005226.12	c.1211-1134G>T		intron_variant		5	NM_153676.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1441376 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 714748

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
Cadd	Benign	18
Dann	Uncertain	0.99
DEOGEN2	Benign	0.12	T;.;.
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.30
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.65	T;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.23	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;.;.
MutationTaster	Benign	1.0	D;N;N;N
PROVEAN	Benign	-1.2	N;N;N
REVEL	Benign	0.12
Sift	Benign	0.043	D;D;T
Sift4G	Uncertain	0.019	D;D;D
Polyphen		0.97	D;.;P
Vest4		0.37
MutPred		0.29		Loss of glycosylation at T422 (P = 0.2104);.;.;
MVP		0.46
ClinPred		0.21	T
GERP RS		3.6
Varity_R		0.12

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs115931035; hg19: chr11-17538971;