rs753080270
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_173477.5(USH1G):c.806G>A(p.Arg269Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000343 in 1,458,824 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
USH1G
NM_173477.5 missense
NM_173477.5 missense
Scores
2
6
8
Clinical Significance
Conservation
PhyloP100: 6.16
Genes affected
USH1G (HGNC:16356): (USH1 protein network component sans) This gene encodes a protein that contains three ankyrin domains, a class I PDZ-binding motif and a sterile alpha motif. The encoded protein interacts with harmonin, which is associated with Usher syndrome type 1C. This protein plays a role in the development and maintenance of the auditory and visual systems and functions in the cohesion of hair bundles formed by inner ear sensory cells. Mutations in this gene are associated with Usher syndrome type 1G (USH1G). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]
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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 |
---|---|---|---|---|---|---|---|---|
USH1G | NM_173477.5 | c.806G>A | p.Arg269Gln | missense_variant | 2/3 | ENST00000614341.5 | NP_775748.2 | |
USH1G | NM_001282489.3 | c.497G>A | p.Arg166Gln | missense_variant | 2/3 | NP_001269418.1 | ||
USH1G | XM_011524296.2 | c.497G>A | p.Arg166Gln | missense_variant | 2/3 | XP_011522598.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
USH1G | ENST00000614341.5 | c.806G>A | p.Arg269Gln | missense_variant | 2/3 | 1 | NM_173477.5 | ENSP00000480279.1 | ||
USH1G | ENST00000579243.1 | n.*405G>A | non_coding_transcript_exon_variant | 2/3 | 2 | ENSP00000462568.1 | ||||
USH1G | ENST00000579243.1 | n.*405G>A | 3_prime_UTR_variant | 2/3 | 2 | ENSP00000462568.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000343 AC: 5AN: 1458824Hom.: 0 Cov.: 42 AF XY: 0.00000551 AC XY: 4AN XY: 725854
GnomAD4 exome
AF:
AC:
5
AN:
1458824
Hom.:
Cov.:
42
AF XY:
AC XY:
4
AN XY:
725854
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
Bravo
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ExAC
AF:
AC:
1
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jul 06, 2015 | The p.Arg269Gln variant in USH1G has not been previously reported in individuals with hearing loss or Usher syndrome, but has been identified in 1/64314 Europea n chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstit ute.org; dbSNP rs753080270). Although this variant has been seen in the general population, its frequency is not high enough to rule out a pathogenic role. Comp utational prediction tools and conservation analysis do not provide strong suppo rt for or against an impact to the protein. In summary, the clinical significanc e of the p.Arg269Gln variant is uncertain. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Pathogenic
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationAssessor
Benign
L
PrimateAI
Uncertain
T
Sift4G
Benign
T
Polyphen
P
Vest4
MutPred
Loss of helix (P = 3e-04);
MVP
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at