rs4806942

Variant names:

• chr19-3589341-G-A
• rs4806942
• NM_133261.3:c.593-102G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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]

GIPC3 Gene-Disease associations (from GenCC):

• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• autosomal recessive nonsyndromic hearing loss 15

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133261.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GIPC3	NM_133261.3	MANE Select	c.593-102G>A		intron	N/A	NP_573568.1
	GIPC3	NM_001411144.1		c.593-102G>A		intron	N/A	NP_001398073.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GIPC3	ENST00000644452.3	MANE Select	c.593-102G>A		intron	N/A	ENSP00000493901.2
	GIPC3	ENST00000644946.1		c.593-102G>A		intron	N/A	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

African (AFR) AF: 0.0908 AC: 1690 AN: 18612

American (AMR) AF: 0.224 AC: 8905 AN: 39842

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 3610 AN: 20954

East Asian (EAS) AF: 0.424 AC: 15094 AN: 35612

South Asian (SAS) AF: 0.0748 AC: 5113 AN: 68394

European-Finnish (FIN) AF: 0.110 AC: 5486 AN: 49750

Middle Eastern (MID) AF: 0.114 AC: 487 AN: 4286

European-Non Finnish (NFE) AF: 0.136 AC: 55188 AN: 404958

Other (OTH) AF: 0.146 AC: 5060 AN: 34772

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

African (AFR) AF: 0.0933 AC: 3876 AN: 41540

American (AMR) AF: 0.167 AC: 2555 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 592 AN: 3472

East Asian (EAS) AF: 0.444 AC: 2290 AN: 5158

South Asian (SAS) AF: 0.0845 AC: 408 AN: 4828

European-Finnish (FIN) AF: 0.105 AC: 1113 AN: 10622

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.133 AC: 9063 AN: 67968

Other (OTH) AF: 0.140 AC: 296 AN: 2108

Alfa AF: 0.137 Hom.: 1300

Bravo AF: 0.142

Asia WGS AF: 0.226 AC: 785 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	15
DANN	Benign	0.93
PhyloP100		2.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4806942; hg19: chr19-3589339; COSMIC: COSV107374258;