10-53902396-C-T

Position:

• chr10-53902396-C-T

Variant summary

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

The NM_001384140.1(PCDH15):​c.3501+847G>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 151,972 control chromosomes in the GnomAD database, including 5,901 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 (5901 hom., cov: 32)
• Consequence: PCDH15 NM_001384140.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.565

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]

PCDH15 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• 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_033056.4	c.3501+847G>A		intron_variant		ENST00000320301.11	NP_149045.3
PCDH15	NM_001384140.1	c.3501+847G>A		intron_variant		ENST00000644397.2	NP_001371069.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCDH15	ENST00000320301.11	c.3501+847G>A		intron_variant		1	NM_033056.4	ENSP00000322604.6
PCDH15	ENST00000644397.2	c.3501+847G>A		intron_variant			NM_001384140.1	ENSP00000495195.1

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34292 AN: 151854 Hom.: 5892 Cov.: 32

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.356

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.226 AC: 34350 AN: 151972 Hom.: 5901 Cov.: 32 AF XY: 0.226 AC XY: 16821 AN XY: 74298

Gnomad4 AFR AF: 0.473

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.127

Gnomad4 EAS AF: 0.356

Gnomad4 SAS AF: 0.218

Gnomad4 FIN AF: 0.109

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.210

Alfa AF: 0.123 Hom.: 2360

Bravo AF: 0.240

Asia WGS AF: 0.342 AC: 1184 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.8
DANN	Benign	0.80

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: rs11003924; hg19: chr10-55662156;