10-53902466-G-T

Position:

• chr10-53902466-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033056.4(PCDH15):​c.3501+777C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 152,032 control chromosomes in the GnomAD database, including 5,899 homozygotes. 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 0.23 (5899 hom., cov: 32)
• Consequence: PCDH15 NM_033056.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00200

Genes affected

PCDH15 (HGNC:14674): (protocadherin related 15) This gene is a member of the cadherin superfamily. Family members encode integral membrane proteins that mediate calcium-dependent cell-cell adhesion. It plays an essential role in maintenance of normal retinal and cochlear function. Mutations in this gene result in hearing loss and Usher Syndrome Type IF (USH1F). Extensive alternative splicing resulting in multiple isoforms has been observed in the mouse ortholog. Similar alternatively spliced transcripts are inferred to occur in human, and additional variants are likely to occur. [provided by RefSeq, Dec 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCDH15	NM_001384140.1	c.3501+777C>A		intron_variant		ENST00000644397.2	NP_001371069.1
PCDH15	NM_033056.4	c.3501+777C>A		intron_variant		ENST00000320301.11	NP_149045.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCDH15	ENST00000320301.11	c.3501+777C>A		intron_variant		1	NM_033056.4	ENSP00000322604
PCDH15	ENST00000644397.2	c.3501+777C>A		intron_variant			NM_001384140.1	ENSP00000495195

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34291 AN: 151914 Hom.: 5890 Cov.: 32

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.356

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.205

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.226 AC: 34349 AN: 152032 Hom.: 5899 Cov.: 32 AF XY: 0.226 AC XY: 16816 AN XY: 74326

Gnomad4 AFR AF: 0.473

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.127

Gnomad4 EAS AF: 0.356

Gnomad4 SAS AF: 0.217

Gnomad4 FIN AF: 0.109

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.210

Alfa AF: 0.136 Hom.: 1043

Bravo AF: 0.240

Asia WGS AF: 0.341 AC: 1181 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.8
DANN	Benign	0.64

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

Publications

LitVar

Other links and lift over

dbSNP: rs11003925; hg19: chr10-55662226;