rs80060313

Variant names:

• chr19-3585729-G-C
• rs80060313
• NM_133261.3:c.132G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-3585729-G-C
• chr19-3585729-G-T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS1

The NM_133261.3(GIPC3):​c.132G>C​(p.Ala44Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000312 in 1,531,040 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0017 (1 hom., cov: 31)
  • Exomes 𝑓: 0.00016 (0 hom.)
• Consequence: GIPC3 NM_133261.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.645
• 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: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 19-3585729-G-C is Benign according to our data. Variant chr19-3585729-G-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 227377.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.645 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0017 (258/152090) while in subpopulation AFR AF = 0.00602 (250/41536). AF 95% confidence interval is 0.00541. There are 1 homozygotes in GnomAd4. There are 112 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

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.132G>C	p.Ala44Ala	synonymous	Exon 1 of 6	NP_573568.1
	GIPC3	NM_001411144.1		c.132G>C	p.Ala44Ala	synonymous	Exon 1 of 6	NP_001398073.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GIPC3	ENST00000644452.3	MANE Select	c.132G>C	p.Ala44Ala	synonymous	Exon 1 of 6	ENSP00000493901.2
	GIPC3	ENST00000644946.1		c.132G>C	p.Ala44Ala	synonymous	Exon 1 of 6	ENSP00000495068.1
	GIPC3	ENST00000854561.1		c.132G>C	p.Ala44Ala	synonymous	Exon 1 of 6	ENSP00000524620.1

Frequencies

GnomAD3 genomes AF: 0.00169 AC: 257 AN: 151980 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.00601

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

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: 0.00

Gnomad OTH AF: 0.000959

GnomAD2 exomes AF: 0.000210 AC: 27 AN: 128644 AF XY: 0.000170

Gnomad AFR exome AF: 0.00545

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000428

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000159 AC: 219 AN: 1378950 Hom.: 0 Cov.: 31 AF XY: 0.000135 AC XY: 92 AN XY: 680308

African (AFR) AF: 0.00656 AC: 196 AN: 29878

American (AMR) AF: 0.0000867 AC: 3 AN: 34600

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24662

East Asian (EAS) AF: 0.00 AC: 0 AN: 33410

South Asian (SAS) AF: 0.00 AC: 0 AN: 77594

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46218

Middle Eastern (MID) AF: 0.000392 AC: 2 AN: 5108

European-Non Finnish (NFE) AF: 0.00000187 AC: 2 AN: 1070396

Other (OTH) AF: 0.000280 AC: 16 AN: 57084

GnomAD4 genome AF: 0.00170 AC: 258 AN: 152090 Hom.: 1 Cov.: 31 AF XY: 0.00151 AC XY: 112 AN XY: 74350

African (AFR) AF: 0.00602 AC: 250 AN: 41536

American (AMR) AF: 0.000392 AC: 6 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10532

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67954

Other (OTH) AF: 0.000949 AC: 2 AN: 2108

Alfa AF: 0.000543 Hom.: 0

Bravo AF: 0.00181

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	8.4
DANN	Benign	0.90
PhyloP100		-0.65
PromoterAI		0.037	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: rs80060313; hg19: chr19-3585727;