10-54536060-C-T

Position:

• chr10-54536060-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.92-8183G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 151,920 control chromosomes in the GnomAD database, including 6,759 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 0.28 (6759 hom., cov: 32)
• Consequence: PCDH15 NM_001384140.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42

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]

ENSG00000234173 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.422 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCDH15	NM_033056.4	c.92-8183G>A		intron_variant		ENST00000320301.11	NP_149045.3
PCDH15	NM_001384140.1	c.92-8183G>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.92-8183G>A		intron_variant		1	NM_033056.4	ENSP00000322604.6
PCDH15	ENST00000644397.2	c.92-8183G>A		intron_variant			NM_001384140.1	ENSP00000495195.1

Frequencies

GnomAD3 genomes AF: 0.283 AC: 42966 AN: 151802 Hom.: 6746 Cov.: 32

Gnomad AFR AF: 0.407

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.438

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.258

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

GnomAD4 genome AF: 0.283 AC: 43007 AN: 151920 Hom.: 6759 Cov.: 32 AF XY: 0.284 AC XY: 21067 AN XY: 74262

Gnomad4 AFR AF: 0.408

Gnomad4 AMR AF: 0.264

Gnomad4 ASJ AF: 0.192

Gnomad4 EAS AF: 0.437

Gnomad4 SAS AF: 0.293

Gnomad4 FIN AF: 0.234

Gnomad4 NFE AF: 0.214

Gnomad4 OTH AF: 0.256

Alfa AF: 0.227 Hom.: 8330

Bravo AF: 0.293

Asia WGS AF: 0.344 AC: 1195 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.17
DANN	Benign	0.21

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: rs1758827; hg19: chr10-56295820;