11-17501143-G-T

Variant names:

• chr11-17501143-G-T
• NM_153676.4:c.2288C>A

Variant summary

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

The NM_153676.4(USH1C):​c.2288C>A​(p.Ser763Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,224 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: USH1C NM_153676.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.77

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USH1C	NM_153676.4	c.2288C>A	p.Ser763Tyr	missense_variant	Exon 23 of 27	ENST00000005226.12	NP_710142.1
USH1C	NM_005709.4	c.1388C>A	p.Ser463Tyr	missense_variant	Exon 18 of 21	ENST00000318024.9	NP_005700.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USH1C	ENST00000005226.12	c.2288C>A	p.Ser763Tyr	missense_variant	Exon 23 of 27	5	NM_153676.4	ENSP00000005226.7
USH1C	ENST00000318024.9	c.1388C>A	p.Ser463Tyr	missense_variant	Exon 18 of 21	1	NM_005709.4	ENSP00000317018.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461224 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 726890

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.32	T;.;.;.
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.94	D;D;D;D
M_CAP	Benign	0.0082	T
MetaRNN	Uncertain	0.47	T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.3	M;.;.;.
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-2.5	N;D;D;N
REVEL	Benign	0.11
Sift	Benign	0.053	T;T;D;D
Sift4G	Uncertain	0.016	D;D;D;D
Polyphen		0.55	P;.;P;.
Vest4		0.42
MutPred		0.63		Loss of disorder (P = 0.027);.;.;.;
MVP		0.65
MPC		0.30
ClinPred		0.97	D
GERP RS		5.3
Varity_R		0.22
gMVP		0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: chr11-17522690; COSMIC: COSV104523796; COSMIC: COSV104523796;