chr19-3585663-C-T
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_133261.3(GIPC3):c.66C>T(p.Pro22=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000433 in 1,246,726 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 (★★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000047 ( 0 hom. )
Consequence
GIPC3
NM_133261.3 synonymous
NM_133261.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.790
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 -11 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.52).
BP6
Variant 19-3585663-C-T is Benign according to our data. Variant chr19-3585663-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 517599.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.79 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GIPC3 | NM_133261.3 | c.66C>T | p.Pro22= | synonymous_variant | 1/6 | ENST00000644452.3 | |
GIPC3 | NM_001411144.1 | c.66C>T | p.Pro22= | synonymous_variant | 1/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GIPC3 | ENST00000644452.3 | c.66C>T | p.Pro22= | synonymous_variant | 1/6 | NM_133261.3 | P1 | ||
GIPC3 | ENST00000644946.1 | c.66C>T | p.Pro22= | synonymous_variant | 1/6 |
Frequencies
GnomAD3 genomes AF: 0.0000199 AC: 3AN: 150978Hom.: 0 Cov.: 31
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GnomAD4 exome AF: 0.0000465 AC: 51AN: 1095748Hom.: 0 Cov.: 30 AF XY: 0.0000569 AC XY: 30AN XY: 527164
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GnomAD4 genome AF: 0.0000199 AC: 3AN: 150978Hom.: 0 Cov.: 31 AF XY: 0.0000271 AC XY: 2AN XY: 73702
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2024 | GIPC3: BP4, BP7 - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | May 27, 2022 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Oct 24, 2017 | p.Pro22Pro 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. - |
Computational scores
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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