chr19-3585521-G-A

Position:

• chr19-3585521-G-A

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_133261.3(GIPC3):​c.-77G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 1,070,242 control chromosomes in the GnomAD database, including 6,100 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.090 (650 hom., cov: 31)
  • Exomes 𝑓: 0.11 (5450 hom.)
• Consequence: GIPC3 NM_133261.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.77

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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 19-3585521-G-A is Benign according to our data. Variant chr19-3585521-G-A is described in ClinVar as [Benign]. Clinvar id is 1237719.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GIPC3	NM_133261.3	c.-77G>A		5_prime_UTR_variant	1/6	ENST00000644452.3
GIPC3	NM_001411144.1	c.-77G>A		5_prime_UTR_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GIPC3	ENST00000644452.3	c.-77G>A		5_prime_UTR_variant	1/6		NM_133261.3	P1

Frequencies

GnomAD3 genomes AF: 0.0897 AC: 13637 AN: 151978 Hom.: 649 Cov.: 31

Gnomad AFR AF: 0.0821

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0662

Gnomad ASJ AF: 0.0813

Gnomad EAS AF: 0.0518

Gnomad SAS AF: 0.0788

Gnomad FIN AF: 0.0751

Gnomad MID AF: 0.0732

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.0856

GnomAD4 exome AF: 0.107 AC: 98501 AN: 918150 Hom.: 5450 Cov.: 19 AF XY: 0.107 AC XY: 46156 AN XY: 430992

Gnomad4 AFR exome AF: 0.0831

Gnomad4 AMR exome AF: 0.0653

Gnomad4 ASJ exome AF: 0.0712

Gnomad4 EAS exome AF: 0.0506

Gnomad4 SAS exome AF: 0.0810

Gnomad4 FIN exome AF: 0.0742

Gnomad4 NFE exome AF: 0.110

Gnomad4 OTH exome AF: 0.107

GnomAD4 genome AF: 0.0897 AC: 13642 AN: 152092 Hom.: 650 Cov.: 31 AF XY: 0.0868 AC XY: 6452 AN XY: 74352

Gnomad4 AFR AF: 0.0821

Gnomad4 AMR AF: 0.0662

Gnomad4 ASJ AF: 0.0813

Gnomad4 EAS AF: 0.0518

Gnomad4 SAS AF: 0.0789

Gnomad4 FIN AF: 0.0751

Gnomad4 NFE AF: 0.107

Gnomad4 OTH AF: 0.0847

Alfa AF: 0.0239 Hom.: 23

Bravo AF: 0.0885

Asia WGS AF: 0.0770 AC: 265 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 24, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	20
DANN	Uncertain	0.98

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs34722692; hg19: chr19-3585519;