rs2108389

Positions:

• chr19-3591592-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001411144.1(GIPC3):​c.2354T>C​(p.Ile785Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 1,232,466 control chromosomes in the GnomAD database, including 191,709 homozygotes. In-silico tool predicts a benign outcome for this variant. 7/8 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.61 (30077 hom., cov: 31)
  • Exomes 𝑓: 0.54 (161632 hom.)
• Consequence: GIPC3 NM_001411144.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.432

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0012926161).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GIPC3	NM_133261.3	c.*1402T>C		3_prime_UTR_variant	6/6	ENST00000644452.3	NP_573568.1
GIPC3	NM_001411144.1	c.2354T>C	p.Ile785Thr	missense_variant	6/6		NP_001398073.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GIPC3	ENST00000644452.3	c.*1402T>C		3_prime_UTR_variant	6/6		NM_133261.3	ENSP00000493901.2
GIPC3	ENST00000644946.1	c.2354T>C	p.Ile785Thr	missense_variant	6/6			ENSP00000495068.1

Frequencies

GnomAD3 genomes AF: 0.605 AC: 91802 AN: 151714 Hom.: 30033 Cov.: 31

Gnomad AFR AF: 0.847

Gnomad AMI AF: 0.320

Gnomad AMR AF: 0.499

Gnomad ASJ AF: 0.561

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.511

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.552

Gnomad OTH AF: 0.607

GnomAD4 exome AF: 0.541 AC: 584530 AN: 1080634 Hom.: 161632 Cov.: 58 AF XY: 0.540 AC XY: 275531 AN XY: 510360

Gnomad4 AFR exome AF: 0.865

Gnomad4 AMR exome AF: 0.448

Gnomad4 ASJ exome AF: 0.551

Gnomad4 EAS exome AF: 0.174

Gnomad4 SAS exome AF: 0.395

Gnomad4 FIN exome AF: 0.515

Gnomad4 NFE exome AF: 0.548

Gnomad4 OTH exome AF: 0.527

GnomAD4 genome AF: 0.605 AC: 91900 AN: 151832 Hom.: 30077 Cov.: 31 AF XY: 0.597 AC XY: 44285 AN XY: 74170

Gnomad4 AFR AF: 0.847

Gnomad4 AMR AF: 0.499

Gnomad4 ASJ AF: 0.561

Gnomad4 EAS AF: 0.164

Gnomad4 SAS AF: 0.371

Gnomad4 FIN AF: 0.511

Gnomad4 NFE AF: 0.552

Gnomad4 OTH AF: 0.604

Alfa AF: 0.558 Hom.: 38070

Bravo AF: 0.611

TwinsUK AF: 0.542 AC: 2008

ALSPAC AF: 0.549 AC: 2116

Asia WGS AF: 0.353 AC: 1230 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.95
DANN	Benign	0.51
FATHMM_MKL	Benign	0.0094	N
LIST_S2	Benign	0.22	T
MetaRNN	Benign	0.0013	T
GERP RS		-1.4

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: rs2108389; hg19: chr19-3591590; COSMIC: COSV59258898; COSMIC: COSV59258898;