Variant chr13-66631388-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_203487.3(PCDH9):c.3162T>C(p.His1054His) variant causes a synonymous change. The variant allele was found at a frequency of 0.00333 in 1,610,806 control chromosomes in the GnomAD database, including 193 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0042 ( 20 hom., cov: 32)

Exomes 𝑓: 0.0032 ( 173 hom. )

Consequence

PCDH9
NM_203487.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.00

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:

LOC105370247 (HGNC:):

LOC105370247 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 13-66631388-A-G is Benign according to our data. Variant chr13-66631388-A-G is described in ClinVar as [Benign]. Clinvar id is 780154.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0743 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCDH9	NM_203487.3 link	c.3162T>C	p.His1054His	synonymous_variant	4/5	ENST00000377865.7	NP_982354.1	Q9HC56-1X5D7N0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCDH9	ENST00000377865.7 link	c.3162T>C	p.His1054His	synonymous_variant	4/5	1	NM_203487.3	ENSP00000367096.2		Q9HC56-1

Frequencies

GnomAD3 genomes

AF:

0.00423

AC:

644

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00404

Gnomad EAS

AF:

0.0814

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.0147

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00806

AC:

2024

AN:

251240

Hom.:

AF XY:

0.00764

AC XY:

1038

AN XY:

135782

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00377

Gnomad EAS exome

AF:

0.0846

Gnomad SAS exome

AF:

0.00170

Gnomad FIN exome

AF:

0.0140

Gnomad NFE exome

AF:

0.000405

Gnomad OTH exome

AF:

0.00359

GnomAD4 exome

AF:

0.00324

AC:

4730

AN:

1458522

Hom.:

173

Cov.:

AF XY:

0.00326

AC XY:

2364

AN XY:

725932

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.00341

Gnomad4 EAS exome

AF:

0.0834

Gnomad4 SAS exome

AF:

0.00226

Gnomad4 FIN exome

AF:

0.0127

Gnomad4 NFE exome

AF:

0.000157

Gnomad4 OTH exome

AF:

0.00446

GnomAD4 genome

AF:

0.00419

AC:

638

AN:

152284

Hom.:

Cov.:

AF XY:

0.00555

AC XY:

413

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00404

Gnomad4 EAS

AF:

0.0807

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.0147

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000785

Hom.:

Bravo

AF:

0.00395

Asia WGS

AF:

0.0260

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 11, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

7.9

DANN

Benign

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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