Variant 10-53822354-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000320301.11(PCDH15):c.5372C>A(p.Pro1791His) variant causes a missense change. The variant allele was found at a frequency of 0.0000021 in 1,428,102 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P1791L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

PCDH15
ENST00000320301.11 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.66

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16293609).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCDH15	NM_033056.4 linkuse as main transcript	c.5372C>A	p.Pro1791His	missense_variant	33/33	ENST00000320301.11	NP_149045.3
PCDH15	NM_001384140.1 linkuse as main transcript	c.4368-2124C>A		intron_variant		ENST00000644397.2	NP_001371069.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCDH15	ENST00000320301.11 linkuse as main transcript	c.5372C>A	p.Pro1791His	missense_variant	33/33	1	NM_033056.4	ENSP00000322604		Q96QU1-1
PCDH15	ENST00000644397.2 linkuse as main transcript	c.4368-2124C>A		intron_variant			NM_001384140.1	ENSP00000495195

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000522

AC:

AN:

191604

Hom.:

AF XY:

0.00000971

AC XY:

AN XY:

102950

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000370

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000210

AC:

AN:

1428102

Hom.:

Cov.:

AF XY:

0.00000283

AC XY:

AN XY:

707740

show subpopulations

Gnomad4 AFR exome

AF:

0.0000309

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000240

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.39

CADD

Benign

1.7

DANN

Benign

0.84

DEOGEN2

Benign

0.013

.;T;.;.;.;.;.;.;T

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.090

LIST_S2

Benign

0.72

T;T;T;T;T;T;T;T;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.16

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

.;.;.;.;.;.;.;.;L

MutationTaster

Benign

1.0

N;N;N;N;N;N;N;N;N;N;N;N;N;N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.69

N;.;.;N;N;N;.;N;N

REVEL

Benign

0.10

Sift

Uncertain

0.0030

D;.;.;D;D;D;.;D;D

Sift4G

Uncertain

0.012

D;D;D;D;D;D;D;D;D

Polyphen

0.95

P;.;.;P;P;P;.;P;P

Vest4

0.30

MutPred

0.17

.;.;.;Loss of glycosylation at P1793 (P = 0.0207);.;.;.;.;.;

MVP

0.70

MPC

0.030

ClinPred

0.22

GERP RS

1.6

Varity_R

0.059

gMVP

0.25

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over