rs1214727223

Variant names:

• chr19-3585583-C-G
• rs1214727223
• NM_133261.3:c.-15C>G

Your query was ambiguous. Multiple possible variants found:

• chr19-3585583-C-G
• chr19-3585583-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_133261.3(GIPC3):​c.-15C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000001 in 995,588 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000010 (0 hom.)
• Consequence: GIPC3 NM_133261.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GIPC3	NM_133261.3	c.-15C>G		5_prime_UTR_variant	Exon 1 of 6	ENST00000644452.3	NP_573568.1
GIPC3	NM_001411144.1	c.-15C>G		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	ENST00000644452.3	c.-15C>G		5_prime_UTR_variant	Exon 1 of 6		NM_133261.3	ENSP00000493901.2
GIPC3	ENST00000644946.1	c.-15C>G		upstream_gene_variant				ENSP00000495068.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000100 AC: 1 AN: 995588 Hom.: 0 Cov.: 30 AF XY: 0.00000213 AC XY: 1 AN XY: 469446

African (AFR) AF: 0.00 AC: 0 AN: 19822

American (AMR) AF: 0.00 AC: 0 AN: 5720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10518

East Asian (EAS) AF: 0.00 AC: 0 AN: 18118

South Asian (SAS) AF: 0.00 AC: 0 AN: 18754

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 16196

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2444

European-Non Finnish (NFE) AF: 0.00000115 AC: 1 AN: 866550

Other (OTH) AF: 0.00 AC: 0 AN: 37466

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	7.6
DANN	Benign	0.88
PhyloP100		-1.3
PromoterAI		0.24	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: rs1214727223; hg19: chr19-3585581;