19-3585552-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The NM_133261.3(GIPC3):c.-46G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00164 in 1,119,220 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0079 (22 hom., cov: 31)
  • Exomes 𝑓: 0.00066 (5 hom.)
• Consequence: GIPC3 NM_133261.3 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.529

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 19-3585552-G-C is Benign according to our data. Variant chr19-3585552-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1202043.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00789 (1199/151972) while in subpopulation AFR AF= 0.0274 (1139/41520). AF 95% confidence interval is 0.0261. There are 22 homozygotes in gnomad4. There are 588 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GIPC3	NM_133261.3	c.-46G>C		5_prime_UTR_variant	1/6	ENST00000644452.3
GIPC3	NM_001411144.1	c.-46G>C		5_prime_UTR_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GIPC3	ENST00000644452.3	c.-46G>C		5_prime_UTR_variant	1/6		NM_133261.3	P1
GIPC3	ENST00000644946.1			upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.00786 AC: 1194 AN: 151864 Hom.: 22 Cov.: 31

Gnomad AFR AF: 0.0274

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00249

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: 0.000177

Gnomad OTH AF: 0.00478

GnomAD4 exome AF: 0.000661 AC: 639 AN: 967248 Hom.: 5 Cov.: 30 AF XY: 0.000595 AC XY: 271 AN XY: 455342

Gnomad4 AFR exome AF: 0.0262

Gnomad4 AMR exome AF: 0.00197

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000544

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000733

Gnomad4 OTH exome AF: 0.00173

GnomAD4 genome AF: 0.00789 AC: 1199 AN: 151972 Hom.: 22 Cov.: 31 AF XY: 0.00792 AC XY: 588 AN XY: 74282

Gnomad4 AFR AF: 0.0274

Gnomad4 AMR AF: 0.00249

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000177

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00119 Hom.: 1

Bravo AF: 0.00880

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 10, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
Cadd	Benign	16
Dann	Benign	0.85

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs545605260; hg19: chr19-3585550;