11-17496805-G-C

Variant summary

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

The NM_153676.4(USH1C):​c.2499C>G​(p.Ile833Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. I833I) has been classified as Benign.

Frequency

Genomes: not found (cov: 33)

Consequence

USH1C
NM_153676.4 missense

Scores

1
5
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.917
Variant links:
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]

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ACMG classification

Classification made for transcript

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
USH1CNM_153676.4 linkc.2499C>G p.Ile833Met missense_variant Exon 25 of 27 ENST00000005226.12 NP_710142.1 Q9Y6N9-5
USH1CNM_005709.4 linkc.1599C>G p.Ile533Met missense_variant Exon 20 of 21 ENST00000318024.9 NP_005700.2 Q9Y6N9-1A0A0S2Z4U9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
USH1CENST00000005226.12 linkc.2499C>G p.Ile833Met missense_variant Exon 25 of 27 5 NM_153676.4 ENSP00000005226.7 Q9Y6N9-5
USH1CENST00000318024.9 linkc.1599C>G p.Ile533Met missense_variant Exon 20 of 21 1 NM_005709.4 ENSP00000317018.4 Q9Y6N9-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.40
CADD
Benign
14
DANN
Uncertain
0.99
DEOGEN2
Benign
0.17
T;.;.;.
Eigen
Benign
-0.20
Eigen_PC
Benign
-0.36
FATHMM_MKL
Benign
0.15
N
LIST_S2
Benign
0.82
T;T;T;T
M_CAP
Benign
0.022
T
MetaRNN
Uncertain
0.47
T;T;T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Uncertain
2.4
M;.;.;.
PrimateAI
Uncertain
0.57
T
PROVEAN
Benign
-0.68
N;N;N;N
REVEL
Benign
0.26
Sift
Uncertain
0.0040
D;D;D;D
Sift4G
Pathogenic
0.0
D;D;D;D
Polyphen
1.0
D;.;D;.
Vest4
0.42
MutPred
0.62
Loss of sheet (P = 0.0126);.;.;.;
MVP
0.59
MPC
0.10
ClinPred
0.96
D
GERP RS
-3.5
Varity_R
0.38
gMVP
0.64

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-17518352; API