rs8113232

Variant names:

• chr19-3586545-G-A
• rs8113232
• NM_133261.3:c.276G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-3586545-G-A
• chr19-3586545-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_133261.3(GIPC3):​c.276G>A​(p.Leu92Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 1,613,494 control chromosomes in the GnomAD database, including 23,097 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (6459 hom., cov: 31)
  • Exomes 𝑓: 0.13 (16638 hom.)
• Consequence: GIPC3 NM_133261.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.913
• Publications: 24 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)
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 19-3586545-G-A is Benign according to our data. Variant chr19-3586545-G-A is described in ClinVar as Benign. ClinVar VariationId is 46571.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.913 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.511 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GIPC3	NM_133261.3	MANE Select	c.276G>A	p.Leu92Leu	synonymous	Exon 2 of 6	NP_573568.1	Q8TF64
	GIPC3	NM_001411144.1		c.276G>A	p.Leu92Leu	synonymous	Exon 2 of 6	NP_001398073.1	A0A2R8Y651

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GIPC3	ENST00000644452.3	MANE Select	c.276G>A	p.Leu92Leu	synonymous	Exon 2 of 6	ENSP00000493901.2	Q8TF64
	GIPC3	ENST00000644946.1		c.276G>A	p.Leu92Leu	synonymous	Exon 2 of 6	ENSP00000495068.1	A0A2R8Y651
	GIPC3	ENST00000854561.1		c.276G>A	p.Leu92Leu	synonymous	Exon 2 of 6	ENSP00000524620.1

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34745 AN: 151990 Hom.: 6432 Cov.: 31

Gnomad AFR AF: 0.517

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.0512

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.0837

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.187

GnomAD2 exomes AF: 0.137 AC: 34256 AN: 250884 AF XY: 0.130

Gnomad AFR exome AF: 0.532

Gnomad AMR exome AF: 0.0816

Gnomad ASJ exome AF: 0.114

Gnomad EAS exome AF: 0.0486

Gnomad FIN exome AF: 0.0874

Gnomad NFE exome AF: 0.126

Gnomad OTH exome AF: 0.123

GnomAD4 exome AF: 0.133 AC: 194965 AN: 1461386 Hom.: 16638 Cov.: 39 AF XY: 0.132 AC XY: 95623 AN XY: 727008

African (AFR) AF: 0.541 AC: 18112 AN: 33472

American (AMR) AF: 0.0878 AC: 3925 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 2951 AN: 26132

East Asian (EAS) AF: 0.0495 AC: 1965 AN: 39700

South Asian (SAS) AF: 0.125 AC: 10822 AN: 86248

European-Finnish (FIN) AF: 0.0897 AC: 4773 AN: 53182

Middle Eastern (MID) AF: 0.147 AC: 849 AN: 5768

European-Non Finnish (NFE) AF: 0.128 AC: 142394 AN: 1111786

Other (OTH) AF: 0.152 AC: 9174 AN: 60380

GnomAD4 genome AF: 0.229 AC: 34820 AN: 152108 Hom.: 6459 Cov.: 31 AF XY: 0.222 AC XY: 16520 AN XY: 74366

African (AFR) AF: 0.517 AC: 21424 AN: 41426

American (AMR) AF: 0.132 AC: 2017 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 423 AN: 3472

East Asian (EAS) AF: 0.0511 AC: 264 AN: 5166

South Asian (SAS) AF: 0.121 AC: 584 AN: 4832

European-Finnish (FIN) AF: 0.0837 AC: 889 AN: 10624

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.128 AC: 8711 AN: 67988

Other (OTH) AF: 0.185 AC: 391 AN: 2110

Alfa AF: 0.151 Hom.: 5684

Bravo AF: 0.244

Asia WGS AF: 0.126 AC: 439 AN: 3478

EpiCase AF: 0.128

EpiControl AF: 0.126

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	2.0
DANN	Benign	0.66
PhyloP100		0.91
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: rs8113232; hg19: chr19-3586543;