rs9564376

Variant names:

• chr13-67166788-G-A
• rs9564376
• NM_203487.3:c.3036+58617C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PCDH9	NM_203487.3	c.3036+58617C>T		intron_variant	Intron 2 of 4	ENST00000377865.7	NP_982354.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCDH9	ENST00000377865.7	c.3036+58617C>T		intron_variant	Intron 2 of 4	1	NM_203487.3	ENSP00000367096.2
PCDH9	ENST00000544246.5	c.3036+58617C>T		intron_variant	Intron 2 of 3	1		ENSP00000442186.2
PCDH9	ENST00000456367.5	c.3036+58617C>T		intron_variant	Intron 2 of 4	1		ENSP00000401699.2

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

African (AFR) AF: 0.539 AC: 22313 AN: 41424

American (AMR) AF: 0.751 AC: 11470 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.892 AC: 3098 AN: 3472

East Asian (EAS) AF: 0.915 AC: 4732 AN: 5170

South Asian (SAS) AF: 0.868 AC: 4189 AN: 4824

European-Finnish (FIN) AF: 0.938 AC: 9962 AN: 10618

Middle Eastern (MID) AF: 0.782 AC: 230 AN: 294

European-Non Finnish (NFE) AF: 0.904 AC: 61447 AN: 68000

Other (OTH) AF: 0.802 AC: 1696 AN: 2116

Alfa AF: 0.866 Hom.: 96644

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
PhyloP100		0.17
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9564376; hg19: chr13-67740920;