rs9564376

Positions:

• chr13-67166788-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_203487.3(PCDH9):​c.3036+58617C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.789 in 152,098 control chromosomes in the GnomAD database, including 49,375 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.79 (49375 hom., cov: 32)
• Consequence: PCDH9 NM_203487.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.175

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.898 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCDH9	NM_203487.3	c.3036+58617C>T		intron_variant		ENST00000377865.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCDH9	ENST00000377865.7	c.3036+58617C>T		intron_variant		1	NM_203487.3
PCDH9	ENST00000456367.5	c.3036+58617C>T		intron_variant		1
PCDH9	ENST00000544246.5	c.3036+58617C>T		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.789 AC: 119904 AN: 151980 Hom.: 49359 Cov.: 32

Gnomad AFR AF: 0.539

Gnomad AMI AF: 0.894

Gnomad AMR AF: 0.751

Gnomad ASJ AF: 0.892

Gnomad EAS AF: 0.915

Gnomad SAS AF: 0.868

Gnomad FIN AF: 0.938

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.904

Gnomad OTH AF: 0.799

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.789 AC: 119952 AN: 152098 Hom.: 49375 Cov.: 32 AF XY: 0.790 AC XY: 58756 AN XY: 74370

Gnomad4 AFR AF: 0.539

Gnomad4 AMR AF: 0.751

Gnomad4 ASJ AF: 0.892

Gnomad4 EAS AF: 0.915

Gnomad4 SAS AF: 0.868

Gnomad4 FIN AF: 0.938

Gnomad4 NFE AF: 0.904

Gnomad4 OTH AF: 0.802

Alfa AF: 0.880 Hom.: 78043

Bravo AF: 0.764

Asia WGS AF: 0.865 AC: 3008 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.5
DANN	Benign	0.57

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

Other links and lift over

dbSNP: rs9564376; hg19: chr13-67740920;