Variant chr13-66903591-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.3051C>A(p.Ser1017Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00151 in 1,507,656 control chromosomes in the GnomAD database, including 10 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 0.0011 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 9 hom. )

Consequence

PCDH9
NM_203487.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.77

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-AS2 (HGNC:39896): (PCDH9 antisense RNA 2)

PCDH9-AS2 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=0.0070990026).

BP6

Variant 13-66903591-G-T is Benign according to our data. Variant chr13-66903591-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2643837.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 174 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCDH9	NM_203487.3 linkuse as main transcript	c.3051C>A	p.Ser1017Arg	missense_variant	3/5	ENST00000377865.7
PCDH9-AS2	NR_046527.1 linkuse as main transcript	n.355-10807G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCDH9	ENST00000377865.7 linkuse as main transcript	c.3051C>A	p.Ser1017Arg	missense_variant	3/5	1	NM_203487.3		Q9HC56-1
PCDH9-AS2	ENST00000419371.2 linkuse as main transcript	n.355-10807G>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00114

AC:

173

AN:

151828

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000723

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00457

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00170

Gnomad OTH

AF:

0.000960

GnomAD3 exomes

AF:

0.00189

AC:

466

AN:

246700

Hom.:

AF XY:

0.00222

AC XY:

297

AN XY:

133514

show subpopulations

Gnomad AFR exome

AF:

0.0000631

Gnomad AMR exome

AF:

0.000952

Gnomad ASJ exome

AF:

0.00242

Gnomad EAS exome

AF:

0.0000552

Gnomad SAS exome

AF:

0.00713

Gnomad FIN exome

AF:

0.0000465

Gnomad NFE exome

AF:

0.00160

Gnomad OTH exome

AF:

0.00235

GnomAD4 exome

AF:

0.00155

AC:

2107

AN:

1355710

Hom.:

Cov.:

AF XY:

0.00176

AC XY:

1200

AN XY:

680262

show subpopulations

Gnomad4 AFR exome

AF:

0.0000968

Gnomad4 AMR exome

AF:

0.000976

Gnomad4 ASJ exome

AF:

0.00277

Gnomad4 EAS exome

AF:

0.0000514

Gnomad4 SAS exome

AF:

0.00697

Gnomad4 FIN exome

AF:

0.000131

Gnomad4 NFE exome

AF:

0.00126

Gnomad4 OTH exome

AF:

0.00167

GnomAD4 genome

AF:

0.00115

AC:

174

AN:

151946

Hom.:

Cov.:

AF XY:

0.000956

AC XY:

AN XY:

74274

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.000722

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00478

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00170

Gnomad4 OTH

AF:

0.000950

Alfa

AF:

0.000774

Hom.:

Bravo

AF:

0.00104

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00151

AC:

ExAC

AF:

0.00203

AC:

246

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Jul 01, 2024

PCDH9: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0072

T;T

Eigen

Benign

-0.029

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.51

T;T

M_CAP

Benign

0.0062

MetaRNN

Benign

0.0071

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

N;.

MutationTaster

Benign

0.87

D;D;D;D

PrimateAI

Benign

0.46

PROVEAN

Benign

0.010

N;.

REVEL

Benign

0.089

Sift

Benign

0.31

T;.

Sift4G

Benign

0.20

T;T

Polyphen

0.83

P;B

Vest4

0.66

MutPred

0.25

Gain of catalytic residue at N1021 (P = 0.0024);Gain of catalytic residue at N1021 (P = 0.0024);

MVP

0.19

ClinPred

0.016

GERP RS

5.5

Varity_R

0.18

gMVP

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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