19-3586967-C-T

Position:

• chr19-3586967-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_133261.3(GIPC3):​c.565C>T​(p.Arg189Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GIPC3 NM_133261.3 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.845

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 Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 19-3586967-C-T is Pathogenic according to our data. Variant chr19-3586967-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 30758.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr19-3586967-C-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GIPC3	NM_133261.3	c.565C>T	p.Arg189Cys	missense_variant	3/6	ENST00000644452.3	NP_573568.1
GIPC3	NM_001411144.1	c.565C>T	p.Arg189Cys	missense_variant	3/6		NP_001398073.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GIPC3	ENST00000644452.3	c.565C>T	p.Arg189Cys	missense_variant	3/6		NM_133261.3	ENSP00000493901.2
GIPC3	ENST00000644946.1	c.565C>T	p.Arg189Cys	missense_variant	3/6			ENSP00000495068.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

Alfa AF: 0.00152 Hom.: 0

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Autosomal recessive nonsyndromic hearing loss 15 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Dec 01, 2011

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.78	D;D;.
Eigen	Benign	0.15
Eigen_PC	Benign	0.020
FATHMM_MKL	Benign	0.50	D
LIST_S2	Uncertain	0.97	.;D;D
M_CAP	Uncertain	0.21	D
MetaRNN	Uncertain	0.62	D;D;D
MetaSVM	Benign	-0.51	T
MutationAssessor	Uncertain	2.7	M;M;.
PrimateAI	Uncertain	0.78	T
PROVEAN	Pathogenic	-5.8	D;.;.
REVEL	Uncertain	0.51
Sift	Uncertain	0.0010	D;.;.
Sift4G	Uncertain	0.0030	D;.;.
Polyphen		1.0	D;D;.
Vest4		0.94
MutPred		0.53		Loss of MoRF binding (P = 0.0028);Loss of MoRF binding (P = 0.0028);Loss of MoRF binding (P = 0.0028);
MVP		0.49
MPC		0.60
ClinPred		0.99	D
GERP RS		2.2
Varity_R		0.64
gMVP		0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs387907002; hg19: chr19-3586965;