GeneBe

rs80060313

Positions:

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 2P and 15B. PM2BP4_ModerateBP6_Very_StrongBP7BS1

The NM_133261.3(GIPC3):ā€‹c.132G>Cā€‹(p.Ala44=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000312 in 1,531,040 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 (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.0017 ( 1 hom., cov: 31)
Exomes š‘“: 0.00016 ( 0 hom. )

Consequence

GIPC3
NM_133261.3 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.645
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.46).
BP6
Variant 19-3585729-G-C is Benign according to our data. Variant chr19-3585729-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 227377.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.645 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0017 (258/152090) while in subpopulation AFR AF= 0.00602 (250/41536). AF 95% confidence interval is 0.00541. There are 1 homozygotes in gnomad4. There are 112 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 Protein UniProt
GIPC3NM_133261.3 linkuse as main transcriptc.132G>C p.Ala44= synonymous_variant 1/6 ENST00000644452.3 NP_573568.1
GIPC3NM_001411144.1 linkuse as main transcriptc.132G>C p.Ala44= synonymous_variant 1/6 NP_001398073.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GIPC3ENST00000644452.3 linkuse as main transcriptc.132G>C p.Ala44= synonymous_variant 1/6 NM_133261.3 ENSP00000493901 P1
GIPC3ENST00000644946.1 linkuse as main transcriptc.132G>C p.Ala44= synonymous_variant 1/6 ENSP00000495068

Frequencies

GnomAD3 genomes
AF:
0.00169
AC:
257
AN:
151980
Hom.:
1
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00601
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000393
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000959
GnomAD3 exomes
AF:
0.000210
AC:
27
AN:
128644
Hom.:
0
AF XY:
0.000170
AC XY:
12
AN XY:
70394
show subpopulations
Gnomad AFR exome
AF:
0.00545
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000428
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000159
AC:
219
AN:
1378950
Hom.:
0
Cov.:
31
AF XY:
0.000135
AC XY:
92
AN XY:
680308
show subpopulations
Gnomad4 AFR exome
AF:
0.00656
Gnomad4 AMR exome
AF:
0.0000867
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000187
Gnomad4 OTH exome
AF:
0.000280
GnomAD4 genome
AF:
0.00170
AC:
258
AN:
152090
Hom.:
1
Cov.:
31
AF XY:
0.00151
AC XY:
112
AN XY:
74350
show subpopulations
Gnomad4 AFR
AF:
0.00602
Gnomad4 AMR
AF:
0.000392
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000949
Alfa
AF:
0.000543
Hom.:
0
Bravo
AF:
0.00181

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:3
Likely benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Likely benign, criteria provided, single submitterclinical testingGeneDxFeb 25, 2021- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpNov 18, 2023- -
not specified Benign:2
Likely benign, criteria provided, single submitterclinical testingEurofins Ntd Llc (ga)Apr 03, 2018- -
Likely benign, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineAug 11, 2015p.Ala44Ala in Exon 01 of GIPC3: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and it is not located within the splice consensus sequence. This variant has been identified in 3/31 8 African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.bro adinstitute.org; dbSNP rs80060313). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.46
CADD
Benign
8.4
DANN
Benign
0.90

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs80060313; hg19: chr19-3585727; API