chr19-3585654-G-T
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS1
The NM_133261.3(GIPC3):c.57G>T(p.Ala19=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000164 in 1,219,268 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00013 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00017 ( 2 hom. )
Consequence
GIPC3
NM_133261.3 synonymous
NM_133261.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.326
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 Benign. Variant got -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.65).
BP6
?
Variant 19-3585654-G-T is Benign according to our data. Variant chr19-3585654-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 262317.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.326 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000133 (20/150920) while in subpopulation SAS AF= 0.00145 (7/4812). AF 95% confidence interval is 0.000683. There are 0 homozygotes in gnomad4. There are 12 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GIPC3 | NM_133261.3 | c.57G>T | p.Ala19= | synonymous_variant | 1/6 | ENST00000644452.3 | |
GIPC3 | NM_001411144.1 | c.57G>T | p.Ala19= | synonymous_variant | 1/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GIPC3 | ENST00000644452.3 | c.57G>T | p.Ala19= | synonymous_variant | 1/6 | NM_133261.3 | P1 | ||
GIPC3 | ENST00000644946.1 | c.57G>T | p.Ala19= | synonymous_variant | 1/6 |
Frequencies
GnomAD3 genomes ? AF: 0.000139 AC: 21AN: 150812Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.000593 AC: 2AN: 3372Hom.: 0 AF XY: 0.000988 AC XY: 2AN XY: 2024
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GnomAD4 exome AF: 0.000168 AC: 180AN: 1068348Hom.: 2 Cov.: 30 AF XY: 0.000212 AC XY: 108AN XY: 510478
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ClinVar
Significance: Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Aug 23, 2017 | p.Ala19Ala in exon 1 of GIPC3: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 0/0 chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP r s754337950). - |
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2023 | GIPC3: BP4, BP7 - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 10, 2024 | - - |
Autosomal recessive nonsyndromic hearing loss 15 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jul 06, 2021 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at