Genetic Variant GIPC3:c.-77G>A (chr19-3585521-G-A) – ACMG Classification: Benign (-18 pts)

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.77

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
GIPC3	NM_133261.3 link	c.-77G>A		5_prime_UTR_variant	Exon 1 of 6	ENST00000644452.3	NP_573568.1	Q8TF64
GIPC3	NM_001411144.1 link	c.-77G>A		5_prime_UTR_variant	Exon 1 of 6		NP_001398073.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GIPC3	ENST00000644452 link	c.-77G>A		5_prime_UTR_variant	Exon 1 of 6		NM_133261.3	ENSP00000493901.2		Q8TF64
GIPC3	ENST00000644946.1 link	c.-77G>A		upstream_gene_variant				ENSP00000495068.1		A0A2R8Y651

Frequencies

GnomAD3 genomes

AF:

0.0897

AC:

13637

AN:

151978

Hom.:

649

Cov.:

show subpopulations

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.:

AF XY:

0.107

AC XY:

46156

AN XY:

430992

show subpopulations

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.:

AF XY:

0.0868

AC XY:

6452

AN XY:

74352

show subpopulations

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.:

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

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 24, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

0.98

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over