rs4806942

Positions:

• chr19-3589341-G-A
• chr19-3589341-G-C
• chr19-3589341-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_133261.3(GIPC3):​c.593-102G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 829,344 control chromosomes in the GnomAD database, including 11,118 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1680 hom., cov: 32)
  • Exomes 𝑓: 0.15 (9438 hom.)
• Consequence: GIPC3 NM_133261.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.67

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 19-3589341-G-A is Benign according to our data. Variant chr19-3589341-G-A is described in ClinVar as [Benign]. Clinvar id is 1265645.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GIPC3	NM_133261.3	c.593-102G>A		intron_variant		ENST00000644452.3	NP_573568.1
GIPC3	NM_001411144.1	c.593-102G>A		intron_variant			NP_001398073.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GIPC3	ENST00000644452.3	c.593-102G>A		intron_variant			NM_133261.3	ENSP00000493901.2
GIPC3	ENST00000644946.1	c.593-102G>A		intron_variant				ENSP00000495068.1

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20386 AN: 152046 Hom.: 1680 Cov.: 32

Gnomad AFR AF: 0.0934

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.444

Gnomad SAS AF: 0.0853

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.143

GnomAD4 exome AF: 0.149 AC: 100633 AN: 677180 Hom.: 9438 AF XY: 0.144 AC XY: 52353 AN XY: 363410

Gnomad4 AFR exome AF: 0.0908

Gnomad4 AMR exome AF: 0.224

Gnomad4 ASJ exome AF: 0.172

Gnomad4 EAS exome AF: 0.424

Gnomad4 SAS exome AF: 0.0748

Gnomad4 FIN exome AF: 0.110

Gnomad4 NFE exome AF: 0.136

Gnomad4 OTH exome AF: 0.146

GnomAD4 genome AF: 0.134 AC: 20379 AN: 152164 Hom.: 1680 Cov.: 32 AF XY: 0.133 AC XY: 9921 AN XY: 74398

Gnomad4 AFR AF: 0.0933

Gnomad4 AMR AF: 0.167

Gnomad4 ASJ AF: 0.171

Gnomad4 EAS AF: 0.444

Gnomad4 SAS AF: 0.0845

Gnomad4 FIN AF: 0.105

Gnomad4 NFE AF: 0.133

Gnomad4 OTH AF: 0.140

Alfa AF: 0.131 Hom.: 801

Bravo AF: 0.142

Asia WGS AF: 0.226 AC: 785 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	15
DANN	Benign	0.93

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

Other links and lift over

dbSNP: rs4806942; hg19: chr19-3589339;