19-3589076-C-G

Variant names:

• chr19-3589076-C-G
• rs10518241
• NM_133261.3:c.593-367C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_133261.3(GIPC3):​c.593-367C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0971 in 152,156 control chromosomes in the GnomAD database, including 836 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.097 (836 hom., cov: 31)
• Consequence: GIPC3 NM_133261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.19
• Publications: 6 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GIPC3	NM_133261.3	c.593-367C>G		intron_variant	Intron 3 of 5	ENST00000644452.3	NP_573568.1
GIPC3	NM_001411144.1	c.593-367C>G		intron_variant	Intron 3 of 5		NP_001398073.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GIPC3	ENST00000644452.3	c.593-367C>G		intron_variant	Intron 3 of 5		NM_133261.3	ENSP00000493901.2
GIPC3	ENST00000644946.1	c.593-367C>G		intron_variant	Intron 3 of 5			ENSP00000495068.1

Frequencies

GnomAD3 genomes AF: 0.0972 AC: 14771 AN: 152038 Hom.: 835 Cov.: 31

Gnomad AFR AF: 0.0522

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.0816

Gnomad EAS AF: 0.0989

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.0848

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0971 AC: 14779 AN: 152156 Hom.: 836 Cov.: 31 AF XY: 0.102 AC XY: 7622 AN XY: 74376

African (AFR) AF: 0.0522 AC: 2168 AN: 41514

American (AMR) AF: 0.103 AC: 1566 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0816 AC: 283 AN: 3470

East Asian (EAS) AF: 0.0985 AC: 510 AN: 5176

South Asian (SAS) AF: 0.202 AC: 973 AN: 4820

European-Finnish (FIN) AF: 0.166 AC: 1755 AN: 10580

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.106 AC: 7209 AN: 68004

Other (OTH) AF: 0.0863 AC: 182 AN: 2110

Alfa AF: 0.0581 Hom.: 75

Bravo AF: 0.0907

Asia WGS AF: 0.157 AC: 546 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.6
DANN	Benign	0.45
PhyloP100		1.2
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: rs10518241; hg19: chr19-3589074;