rs1172324481

Variant names:

• chr19-3590190-G-A
• rs1172324481
• NM_133261.3:c.939G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-3590190-G-A
• chr19-3590190-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001411144.1(GIPC3):​c.952G>A​(p.Val318Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,439,010 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 8/10 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V318L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: GIPC3 NM_001411144.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.491
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14372826).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001411144.1. 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.939G>A	p.Ter313Ter	stop_retained	Exon 6 of 6	NP_573568.1
	GIPC3	NM_001411144.1		c.952G>A	p.Val318Ile	missense	Exon 6 of 6	NP_001398073.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GIPC3	ENST00000644452.3	MANE Select	c.939G>A	p.Ter313Ter	stop_retained	Exon 6 of 6	ENSP00000493901.2
	GIPC3	ENST00000644946.1		c.952G>A	p.Val318Ile	missense	Exon 6 of 6	ENSP00000495068.1
	GIPC3	ENST00000854561.1		c.870G>A	p.Ter290Ter	stop_retained	Exon 6 of 6	ENSP00000524620.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000970 AC: 2 AN: 206230 AF XY: 0.00000895

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000340

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1439010 Hom.: 0 Cov.: 35 AF XY: 0.00000140 AC XY: 1 AN XY: 713706

African (AFR) AF: 0.00 AC: 0 AN: 33158

American (AMR) AF: 0.0000244 AC: 1 AN: 40964

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25570

East Asian (EAS) AF: 0.00 AC: 0 AN: 38832

South Asian (SAS) AF: 0.0000121 AC: 1 AN: 82972

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51184

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4828

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1102104

Other (OTH) AF: 0.00 AC: 0 AN: 59398

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_noAF	Benign	-0.60
CADD	Benign	12
DANN	Benign	0.81
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.22	T
MetaRNN	Benign	0.14	T
PhyloP100		0.49
GERP RS		3.3
Mutation Taster		=100/0	polymorphism

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: rs1172324481; hg19: chr19-3590188;