Genetic Variant GIPC3:c.*15G>T (chr19-3590205-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001411144.1(GIPC3):c.967G>T(p.Ala323Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000211 in 1,422,188 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 8/9 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. A323T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

GIPC3
NM_001411144.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.708

Publications

0 publications found

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 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)
hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

GIPC3 links:

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ACMG classification

Classification was made for transcript

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=0.12056348).

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.*15G>T		3_prime_UTR	Exon 6 of 6	NP_573568.1	Q8TF64
	GIPC3	NM_001411144.1		c.967G>T	p.Ala323Ser	missense	Exon 6 of 6	NP_001398073.1	A0A2R8Y651

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GIPC3	ENST00000644452.3	MANE Select	c.*15G>T		3_prime_UTR	Exon 6 of 6	ENSP00000493901.2	Q8TF64
GIPC3	ENST00000644946.1		c.967G>T	p.Ala323Ser	missense	Exon 6 of 6	ENSP00000495068.1	A0A2R8Y651
GIPC3	ENST00000854561.1		c.*15G>T		3_prime_UTR	Exon 6 of 6	ENSP00000524620.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

183668

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00000211

AC:

AN:

1422188

Hom.:

Cov.:

AF XY:

0.00000284

AC XY:

AN XY:

703778

show subpopulations

African (AFR)

AF:

0.0000305

AC:

AN:

32742

American (AMR)

AF:

0.00

AC:

AN:

38396

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25346

East Asian (EAS)

AF:

0.00

AC:

AN:

37908

South Asian (SAS)

AF:

0.00

AC:

AN:

81484

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50048

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4502

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1092992

Other (OTH)

AF:

0.0000340

AC:

AN:

58770

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_noAF

Benign

-0.82

CADD

Benign

3.6

(source)

DANN

Benign

0.68

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.20

MetaRNN

Benign

0.12

PhyloP100

0.71

GERP RS

1.1

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over