rs727504632
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_133261.3(GIPC3):c.576G>A(p.Gln192=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,612,562 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000011 ( 1 hom. )
Consequence
GIPC3
NM_133261.3 synonymous
NM_133261.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.463
Genes affected
GIPC3 (HGNC:18183): (GIPC PDZ domain containing family member 3) The protein encoded by this gene belongs to the GIPC family. Studies in mice suggest that this gene is required for postnatal maturation of the hair bundle and long-term survival of hair cells and spiral ganglion in the ear. Mutations in this gene are associated with autosomal recessive deafness. [provided by RefSeq, Dec 2011]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.47).
BP6
?
Variant 19-3586978-G-A is Benign according to our data. Variant chr19-3586978-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 179107.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-3586978-G-A is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=0.463 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GIPC3 | NM_133261.3 | c.576G>A | p.Gln192= | synonymous_variant | 3/6 | ENST00000644452.3 | |
GIPC3 | NM_001411144.1 | c.576G>A | p.Gln192= | synonymous_variant | 3/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GIPC3 | ENST00000644452.3 | c.576G>A | p.Gln192= | synonymous_variant | 3/6 | NM_133261.3 | P1 | ||
GIPC3 | ENST00000644946.1 | c.576G>A | p.Gln192= | synonymous_variant | 3/6 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152172Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000162 AC: 4AN: 247016Hom.: 0 AF XY: 0.0000223 AC XY: 3AN XY: 134416
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GnomAD4 exome AF: 0.0000110 AC: 16AN: 1460390Hom.: 1 Cov.: 34 AF XY: 0.0000165 AC XY: 12AN XY: 726484
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152172Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74346
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
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 | Aug 15, 2013 | Gln192Gln in exon 3 of GIPC3: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue, and it is not located with the splice consensus sequence. - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at