rs185551765

Variant names:

• chr19-3585833-C-T
• rs185551765
• NM_133261.3:c.225+11C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-3585833-C-T
• chr19-3585833-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_133261.3(GIPC3):​c.225+11C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00066 in 1,540,254 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0034 (2 hom., cov: 31)
  • Exomes 𝑓: 0.00036 (3 hom.)
• Consequence: GIPC3 NM_133261.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.588
• 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)
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 19-3585833-C-T is Benign according to our data. Variant chr19-3585833-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 178346.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00337 (513/152256) while in subpopulation AFR AF = 0.0119 (493/41560). AF 95% confidence interval is 0.011. There are 2 homozygotes in GnomAd4. There are 258 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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.225+11C>T		intron	N/A	NP_573568.1	Q8TF64
	GIPC3	NM_001411144.1		c.225+11C>T		intron	N/A	NP_001398073.1	A0A2R8Y651

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GIPC3	ENST00000644452.3	MANE Select	c.225+11C>T		intron	N/A	ENSP00000493901.2	Q8TF64
	GIPC3	ENST00000644946.1		c.225+11C>T		intron	N/A	ENSP00000495068.1	A0A2R8Y651
	GIPC3	ENST00000854561.1		c.225+11C>T		intron	N/A	ENSP00000524620.1

Frequencies

GnomAD3 genomes AF: 0.00333 AC: 507 AN: 152142 Hom.: 2 Cov.: 31

Gnomad AFR AF: 0.0118

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000655

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: 0.00479

GnomAD2 exomes AF: 0.000630 AC: 85 AN: 134988 AF XY: 0.000474

Gnomad AFR exome AF: 0.0116

Gnomad AMR exome AF: 0.000414

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000599

Gnomad OTH exome AF: 0.000245

GnomAD4 exome AF: 0.000362 AC: 503 AN: 1387998 Hom.: 3 Cov.: 31 AF XY: 0.000302 AC XY: 207 AN XY: 684912

African (AFR) AF: 0.0140 AC: 437 AN: 31286

American (AMR) AF: 0.000393 AC: 14 AN: 35588

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25020

East Asian (EAS) AF: 0.00 AC: 0 AN: 35272

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79076

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41446

Middle Eastern (MID) AF: 0.000359 AC: 2 AN: 5566

European-Non Finnish (NFE) AF: 0.00000929 AC: 10 AN: 1076994

Other (OTH) AF: 0.000675 AC: 39 AN: 57750

GnomAD4 genome AF: 0.00337 AC: 513 AN: 152256 Hom.: 2 Cov.: 31 AF XY: 0.00347 AC XY: 258 AN XY: 74442

African (AFR) AF: 0.0119 AC: 493 AN: 41560

American (AMR) AF: 0.000654 AC: 10 AN: 15298

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67996

Other (OTH) AF: 0.00474 AC: 10 AN: 2110

Alfa AF: 0.000343 Hom.: 0

Bravo AF: 0.00416

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	4.6
DANN	Benign	0.90
PhyloP100		-0.59
PromoterAI		0.0020	Neutral
Mutation Taster		=100/0	polymorphism

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: rs185551765; hg19: chr19-3585831;