19-3590190-G-C
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4
The NM_133261.3(GIPC3):c.939G>C(p.Ter313Tyrext*?) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Consequence
GIPC3
NM_133261.3 stop_lost
NM_133261.3 stop_lost
Scores
1
2
6
Clinical Significance
Conservation
PhyloP100: 0.491
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 Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Stoplost variant in NM_133261.3 Downstream stopcodon found after 352 codons.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GIPC3 | NM_133261.3 | c.939G>C | p.Ter313Tyrext*? | stop_lost | 6/6 | ENST00000644452.3 | NP_573568.1 | |
GIPC3 | NM_001411144.1 | c.952G>C | p.Val318Leu | missense_variant | 6/6 | NP_001398073.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GIPC3 | ENST00000644452.3 | c.939G>C | p.Ter313Tyrext*? | stop_lost | 6/6 | NM_133261.3 | ENSP00000493901.2 | |||
GIPC3 | ENST00000644946.1 | c.952G>C | p.Val318Leu | missense_variant | 6/6 | ENSP00000495068.1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Cov.: 35
GnomAD4 exome
Cov.:
35
GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
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 | Jun 23, 2016 | Variant classified as Uncertain Significance - Favor Pathogenic. The p.X313Tyrex tX99 variant in GIPC3 has not been previously reported in individuals with heari ng loss. The variant was absent in large population databases, however this indi vidual is Arab and ethnically matched data is not available in these databases t o accurately assess the frequency of this variant in the Arab population. This v ariant is predicted to result in the loss of the native stop codon leading to a 99 amino acid C-terminus extension of the protein. However, the impact of this e xtension on the normal function of the protein is currently unknown. In summary, while there is some suspicion for a pathogenic role given the impact of the var iant, the clinical significance of this variant is uncertain. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
LIST_S2
Benign
T
MetaRNN
Uncertain
D
GERP RS
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