11-17512023-C-T

Position:

• chr11-17512023-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_153676.4(USH1C):​c.1292G>A​(p.Gly431Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: USH1C NM_153676.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.21

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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14365435).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USH1C	NM_153676.4	c.1292G>A	p.Gly431Asp	missense_variant	16/27	ENST00000005226.12	NP_710142.1
USH1C	NM_005709.4	c.1284+5378G>A		intron_variant		ENST00000318024.9	NP_005700.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USH1C	ENST00000005226.12	c.1292G>A	p.Gly431Asp	missense_variant	16/27	5	NM_153676.4	ENSP00000005226
USH1C	ENST00000318024.9	c.1284+5378G>A		intron_variant		1	NM_005709.4	ENSP00000317018	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.060	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	17
DANN	Benign	0.25
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.29	T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	D;D;D;N
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	1.1	N
REVEL	Benign	0.13
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Vest4		0.29
MutPred		0.45		Loss of methylation at K429 (P = 0.0724);
MVP		0.59
MPC		0.079
ClinPred		0.77	D
GERP RS		5.7
gMVP		0.14

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-17533570;