Variant 13-66304742-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_203487.3(PCDH9):c.3627C>A(p.Ser1209Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00308 in 1,612,976 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0031 ( 22 hom. )

Consequence

PCDH9
NM_203487.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.21

Variant links:

Genes affected

PCDH9 (HGNC:8661): (protocadherin 9) This gene encodes a member of the protocadherin family, and cadherin superfamily, of transmembrane proteins containing cadherin domains. These proteins mediate cell adhesion in neural tissues in the presence of calcium. The encoded protein may be involved in signaling at neuronal synaptic junctions. Sharing a characteristic with other protocadherin genes, this gene has a notably large exon that encodes multiple cadherin domains and a transmembrane region. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Nov 2012]

PCDH9 links:

PCDH9-AS1 (HGNC:39897): (PCDH9 antisense RNA 1)

PCDH9-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004679233).

BP6

Variant 13-66304742-G-T is Benign according to our data. Variant chr13-66304742-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2643836.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 406 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCDH9	NM_203487.3 linkuse as main transcript	c.3627C>A	p.Ser1209Arg	missense_variant	5/5	ENST00000377865.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCDH9	ENST00000377865.7 linkuse as main transcript	c.3627C>A	p.Ser1209Arg	missense_variant	5/5	1	NM_203487.3		Q9HC56-1
PCDH9-AS1	ENST00000430861.1 linkuse as main transcript	n.144+728G>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00268

AC:

407

AN:

151986

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000459

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00190

Gnomad ASJ

AF:

0.0147

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00874

Gnomad FIN

AF:

0.000661

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00357

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00403

AC:

1008

AN:

250428

Hom.:

AF XY:

0.00446

AC XY:

603

AN XY:

135340

show subpopulations

Gnomad AFR exome

AF:

0.000554

Gnomad AMR exome

AF:

0.00235

Gnomad ASJ exome

AF:

0.0178

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.00872

Gnomad FIN exome

AF:

0.000418

Gnomad NFE exome

AF:

0.00388

Gnomad OTH exome

AF:

0.00378

GnomAD4 exome

AF:

0.00312

AC:

4560

AN:

1460872

Hom.:

Cov.:

AF XY:

0.00341

AC XY:

2481

AN XY:

726784

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.00265

Gnomad4 ASJ exome

AF:

0.0169

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00830

Gnomad4 FIN exome

AF:

0.000619

Gnomad4 NFE exome

AF:

0.00267

Gnomad4 OTH exome

AF:

0.00384

GnomAD4 genome

AF:

0.00267

AC:

406

AN:

152104

Hom.:

Cov.:

AF XY:

0.00272

AC XY:

202

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.000458

Gnomad4 AMR

AF:

0.00190

Gnomad4 ASJ

AF:

0.0147

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00853

Gnomad4 FIN

AF:

0.000661

Gnomad4 NFE

AF:

0.00357

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.00406

Hom.:

Bravo

AF:

0.00243

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00311

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00256

AC:

ExAC

AF:

0.00400

AC:

485

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00453

EpiControl

AF:

0.00380

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2022

PCDH9: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.011

T;.;T

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.079

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.89

D;D;D

M_CAP

Benign

0.0058

MetaRNN

Benign

0.0047

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

L;.;.

MutationTaster

Benign

0.95

N;N;N;N

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.1

N;.;.

REVEL

Benign

0.067

Sift

Benign

0.036

D;.;.

Sift4G

Benign

0.076

T;T;T

Polyphen

0.013

B;B;B

Vest4

0.33

MutPred

0.32

Gain of catalytic residue at D1213 (P = 0.0028);.;.;

MVP

0.18

MPC

0.34

ClinPred

0.014

GERP RS

4.0

Varity_R

0.10

gMVP

0.43

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over