rs545605260

Variant names:

• chr19-3585552-G-A
• rs545605260
• NM_133261.3:c.-46G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-3585552-G-A
• chr19-3585552-G-C
• chr19-3585552-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_133261.3(GIPC3):​c.-46G>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 0.00000536 in 1,119,116 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000052 (0 hom.)
• Consequence: GIPC3 NM_133261.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.529
• 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: 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 (BayesDel_noAF=-0.38).

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.-46G>A		5_prime_UTR	Exon 1 of 6	NP_573568.1	Q8TF64
	GIPC3	NM_001411144.1		c.-46G>A		5_prime_UTR	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.-46G>A		5_prime_UTR	Exon 1 of 6	ENSP00000493901.2	Q8TF64
	GIPC3	ENST00000854561.1		c.-46G>A		5_prime_UTR	Exon 1 of 6	ENSP00000524620.1
	GIPC3	ENST00000644946.1		c.-46G>A		upstream_gene	N/A	ENSP00000495068.1	A0A2R8Y651

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151866 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000517 AC: 5 AN: 967250 Hom.: 0 Cov.: 30 AF XY: 0.00000439 AC XY: 2 AN XY: 455342

African (AFR) AF: 0.00 AC: 0 AN: 19122

American (AMR) AF: 0.00 AC: 0 AN: 5084

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9766

East Asian (EAS) AF: 0.0000606 AC: 1 AN: 16492

South Asian (SAS) AF: 0.00 AC: 0 AN: 18376

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 14346

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2338

European-Non Finnish (NFE) AF: 0.00000355 AC: 3 AN: 845888

Other (OTH) AF: 0.0000279 AC: 1 AN: 35838

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151866 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74164

African (AFR) AF: 0.00 AC: 0 AN: 41404

American (AMR) AF: 0.00 AC: 0 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10546

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67884

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	16
DANN	Uncertain	0.98
PhyloP100		0.53
PromoterAI		-0.14	Neutral

Splicing

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

Other links and lift over

dbSNP: rs545605260; hg19: chr19-3585550;