chr11-17522838-C-A

Variant summary

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

The ENST00000318024.9(USH1C):​c.965G>T​(p.Arg322Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R322Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

USH1C
ENST00000318024.9 missense

Scores

7
12

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.79
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/exons MANE Protein UniProt
USH1CNM_153676.4 linkuse as main transcriptc.965G>T p.Arg322Leu missense_variant 12/27 ENST00000005226.12 NP_710142.1
USH1CNM_005709.4 linkuse as main transcriptc.965G>T p.Arg322Leu missense_variant 12/21 ENST00000318024.9 NP_005700.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
USH1CENST00000005226.12 linkuse as main transcriptc.965G>T p.Arg322Leu missense_variant 12/275 NM_153676.4 ENSP00000005226 Q9Y6N9-5
USH1CENST00000318024.9 linkuse as main transcriptc.965G>T p.Arg322Leu missense_variant 12/211 NM_005709.4 ENSP00000317018 P1Q9Y6N9-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.22
BayesDel_addAF
Benign
-0.063
T
BayesDel_noAF
Benign
-0.33
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.44
T;.;.;.
Eigen
Benign
-0.11
Eigen_PC
Benign
-0.088
FATHMM_MKL
Uncertain
0.81
D
LIST_S2
Uncertain
0.96
D;D;D;D
M_CAP
Benign
0.043
D
MetaRNN
Uncertain
0.47
T;T;T;T
MetaSVM
Benign
-0.90
T
MutationAssessor
Benign
1.4
L;.;.;L
MutationTaster
Benign
0.55
D;D;D;D
PrimateAI
Benign
0.36
T
PROVEAN
Uncertain
-3.3
D;D;D;D
REVEL
Benign
0.13
Sift
Uncertain
0.0040
D;D;D;D
Sift4G
Benign
0.072
T;T;T;D
Polyphen
0.83
P;.;P;.
Vest4
0.61
MutPred
0.40
Loss of MoRF binding (P = 0.0317);.;.;Loss of MoRF binding (P = 0.0317);
MVP
0.53
MPC
0.090
ClinPred
0.79
D
GERP RS
3.1
Varity_R
0.21
gMVP
0.38

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs140424216; hg19: chr11-17544385; API