rs9285254

Variant names:

• chr13-66425683-A-T
• rs9285254
• NM_203487.3:c.3341-120655T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_203487.3(PCDH9):​c.3341-120655T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 151,492 control chromosomes in the GnomAD database, including 12,497 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 0.40 (12497 hom., cov: 31)
• Consequence: PCDH9 NM_203487.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.450
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCDH9	NM_203487.3	c.3341-120655T>A		intron_variant	Intron 4 of 4	ENST00000377865.7	NP_982354.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCDH9	ENST00000377865.7	c.3341-120655T>A		intron_variant	Intron 4 of 4	1	NM_203487.3	ENSP00000367096.2
PCDH9	ENST00000544246.5	c.3239-120655T>A		intron_variant	Intron 3 of 3	1		ENSP00000442186.2
PCDH9	ENST00000456367.5	c.3215-120655T>A		intron_variant	Intron 4 of 4	1		ENSP00000401699.2
PCDH9	ENST00000614931.1	n.*254-120655T>A		intron_variant	Intron 3 of 3	1		ENSP00000482917.1

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60039 AN: 151374 Hom.: 12501 Cov.: 31

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.415

Gnomad AMR AF: 0.456

Gnomad ASJ AF: 0.442

Gnomad EAS AF: 0.506

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.398

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

GnomAD4 genome AF: 0.396 AC: 60065 AN: 151492 Hom.: 12497 Cov.: 31 AF XY: 0.394 AC XY: 29204 AN XY: 74060

African (AFR) AF: 0.256 AC: 10594 AN: 41434

American (AMR) AF: 0.456 AC: 6912 AN: 15170

Ashkenazi Jewish (ASJ) AF: 0.442 AC: 1528 AN: 3458

East Asian (EAS) AF: 0.507 AC: 2610 AN: 5152

South Asian (SAS) AF: 0.410 AC: 1979 AN: 4824

European-Finnish (FIN) AF: 0.424 AC: 4472 AN: 10554

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.453 AC: 30635 AN: 67592

Other (OTH) AF: 0.398 AC: 839 AN: 2106

Alfa AF: 0.417 Hom.: 1682

Bravo AF: 0.397

Asia WGS AF: 0.443 AC: 1543 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.8
DANN	Benign	0.43
PhyloP100		0.45
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: rs9285254; hg19: chr13-66999815;