rs2032348670

Variant names:

• chr19-3585639-C-T
• rs2032348670
• NM_133261.3:c.42C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_133261.3(GIPC3):​c.42C>T​(p.Thr14Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000096 in 1,041,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 9.6e-7 (0 hom.)
• Consequence: GIPC3 NM_133261.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.507
• Publications: 0 publications found

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), PanelApp Australia
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 19-3585639-C-T is Benign according to our data. Variant chr19-3585639-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3700599.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.507 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133261.3. 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.42C>T	p.Thr14Thr	synonymous	Exon 1 of 6	NP_573568.1	Q8TF64
	GIPC3	NM_001411144.1		c.42C>T	p.Thr14Thr	synonymous	Exon 1 of 6	NP_001398073.1	A0A2R8Y651

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GIPC3	ENST00000644452.3	MANE Select	c.42C>T	p.Thr14Thr	synonymous	Exon 1 of 6	ENSP00000493901.2	Q8TF64
	GIPC3	ENST00000644946.1		c.42C>T	p.Thr14Thr	synonymous	Exon 1 of 6	ENSP00000495068.1	A0A2R8Y651
	GIPC3	ENST00000854561.1		c.42C>T	p.Thr14Thr	synonymous	Exon 1 of 6	ENSP00000524620.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 9.60e-7 AC: 1 AN: 1041818 Hom.: 0 Cov.: 30 AF XY: 0.00000202 AC XY: 1 AN XY: 495476

African (AFR) AF: 0.00 AC: 0 AN: 21034

American (AMR) AF: 0.000149 AC: 1 AN: 6732

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11828

East Asian (EAS) AF: 0.00 AC: 0 AN: 21670

South Asian (SAS) AF: 0.00 AC: 0 AN: 19442

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20534

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2672

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 897822

Other (OTH) AF: 0.00 AC: 0 AN: 40084

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	8.8
DANN	Benign	0.94
PhyloP100		0.51
PromoterAI		-0.047	Neutral

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

Other links and lift over

dbSNP: rs2032348670; hg19: chr19-3585637;