rs773660538
Positions:
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_173477.5(USH1G):āc.972T>Cā(p.Ser324=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000479 in 1,605,918 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.000033 ( 0 hom., cov: 32)
Exomes š: 0.000049 ( 0 hom. )
Consequence
USH1G
NM_173477.5 synonymous
NM_173477.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0850
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.57).
BP6
?
Variant 17-74919864-A-G is Benign according to our data. Variant chr17-74919864-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 228199.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.085 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
USH1G | NM_173477.5 | c.972T>C | p.Ser324= | synonymous_variant | 2/3 | ENST00000614341.5 | |
USH1G | NM_001282489.3 | c.663T>C | p.Ser221= | synonymous_variant | 2/3 | ||
USH1G | XM_011524296.2 | c.663T>C | p.Ser221= | synonymous_variant | 2/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
USH1G | ENST00000614341.5 | c.972T>C | p.Ser324= | synonymous_variant | 2/3 | 1 | NM_173477.5 | P1 | |
USH1G | ENST00000579243.1 | c.*571T>C | 3_prime_UTR_variant, NMD_transcript_variant | 2/3 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000332 AC: 5AN: 150598Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
5
AN:
150598
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000279 AC: 7AN: 250536Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135696
GnomAD3 exomes
AF:
AC:
7
AN:
250536
Hom.:
AF XY:
AC XY:
2
AN XY:
135696
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000495 AC: 72AN: 1455320Hom.: 0 Cov.: 42 AF XY: 0.0000442 AC XY: 32AN XY: 724176
GnomAD4 exome
AF:
AC:
72
AN:
1455320
Hom.:
Cov.:
42
AF XY:
AC XY:
32
AN XY:
724176
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000332 AC: 5AN: 150598Hom.: 0 Cov.: 32 AF XY: 0.0000544 AC XY: 4AN XY: 73532
GnomAD4 genome
?
AF:
AC:
5
AN:
150598
Hom.:
Cov.:
32
AF XY:
AC XY:
4
AN XY:
73532
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 22, 2015 | p.Ser324Ser in exon 2 of USH1G: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 08, 2022 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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