Variant 10-54329622-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_033056.4(PCDH15):c.679C>A(p.Arg227Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PCDH15
NM_033056.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.25

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCDH15	NM_033056.4 linkuse as main transcript	c.679C>A	p.Arg227Ser	missense_variant	7/33	ENST00000320301.11	NP_149045.3
PCDH15	NM_001384140.1 linkuse as main transcript	c.679C>A	p.Arg227Ser	missense_variant	7/38	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.679C>A	p.Arg227Ser	missense_variant	7/33	1	NM_033056.4	ENSP00000322604		Q96QU1-1
PCDH15	ENST00000644397.2 linkuse as main transcript	c.679C>A	p.Arg227Ser	missense_variant	7/38		NM_001384140.1	ENSP00000495195

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1449992

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

722084

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

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

Pathogenic

0.62

BayesDel_addAF

Benign

-0.066

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.050

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

Eigen

Benign

0.15

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.78

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

M_CAP

Benign

0.021

MetaRNN

Uncertain

0.45

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

MetaSVM

Benign

-0.81

MutationAssessor

Benign

0.80

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

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;N

PrimateAI

Uncertain

0.57

PROVEAN

Uncertain

-4.2

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

REVEL

Benign

0.26

Sift

Uncertain

0.0030

D;.;.;.;.;.;T;T;.;T;.;D;D;.;.;.;D;T;D;.;T;D;D

Sift4G

Uncertain

0.0070

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

Polyphen

0.83, 0.95, 0.91, 0.90, 0.45

.;.;.;.;.;.;.;.;.;.;.;.;P;.;.;.;P;P;P;.;P;P;B

Vest4

0.78

MutPred

0.60

Gain of ubiquitination at K225 (P = 0.0561);Gain of ubiquitination at K225 (P = 0.0561);.;Gain of ubiquitination at K225 (P = 0.0561);Gain of ubiquitination at K225 (P = 0.0561);.;Gain of ubiquitination at K225 (P = 0.0561);Gain of ubiquitination at K225 (P = 0.0561);Gain of ubiquitination at K225 (P = 0.0561);Gain of ubiquitination at K225 (P = 0.0561);.;Gain of ubiquitination at K225 (P = 0.0561);Gain of ubiquitination at K225 (P = 0.0561);.;.;Gain of ubiquitination at K225 (P = 0.0561);Gain of ubiquitination at K225 (P = 0.0561);Gain of ubiquitination at K225 (P = 0.0561);.;.;Gain of ubiquitination at K225 (P = 0.0561);Gain of ubiquitination at K225 (P = 0.0561);Gain of ubiquitination at K225 (P = 0.0561);

MVP

0.73

MPC

0.078

ClinPred

0.92

GERP RS

4.5

Varity_R

0.45

gMVP

0.70

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