rs397517877

Variant names:

• chr11-17498211-G-C
• rs397517877
• NM_153676.4:c.2441C>G

Your query was ambiguous. Multiple possible variants found:

• chr11-17498211-G-C
• chr11-17498211-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_153676.4(USH1C):​c.2441C>G​(p.Thr814Ser) 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. 13/21 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: 1.74

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26440662).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USH1C	NM_153676.4	c.2441C>G	p.Thr814Ser	missense_variant	Exon 24 of 27	ENST00000005226.12	NP_710142.1
USH1C	NM_005709.4	c.1541C>G	p.Thr514Ser	missense_variant	Exon 19 of 21	ENST00000318024.9	NP_005700.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USH1C	ENST00000005226.12	c.2441C>G	p.Thr814Ser	missense_variant	Exon 24 of 27	5	NM_153676.4	ENSP00000005226.7
USH1C	ENST00000318024.9	c.1541C>G	p.Thr514Ser	missense_variant	Exon 19 of 21	1	NM_005709.4	ENSP00000317018.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.059	T;.;.;.
Eigen	Benign	-0.018
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.70	T;T;T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.26	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.61	N;.;.;.
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.61	N;N;N;N
REVEL	Benign	0.079
Sift	Benign	0.39	T;T;T;D
Sift4G	Benign	0.38	T;T;T;T
Polyphen		0.0030	B;.;B;.
Vest4		0.35
MutPred		0.56		Gain of disorder (P = 0.1328);.;.;.;
MVP		0.55
MPC		0.097
ClinPred		0.35	T
GERP RS		5.3
Varity_R		0.22
gMVP		0.49

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

LitVar

Other links and lift over

dbSNP: rs397517877; hg19: chr11-17519758;