rs9285254

Positions:

• chr13-66425683-A-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.87).
• 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/exons	MANE	Protein	UniProt
PCDH9	NM_203487.3	c.3341-120655T>A		intron_variant		ENST00000377865.7	NP_982354.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCDH9	ENST00000377865.7	c.3341-120655T>A		intron_variant		1	NM_203487.3	ENSP00000367096
PCDH9	ENST00000456367.5	c.3215-120655T>A		intron_variant		1		ENSP00000401699
PCDH9	ENST00000544246.5	c.3239-120655T>A		intron_variant		1		ENSP00000442186	P1
PCDH9	ENST00000614931.1	c.*254-120655T>A		intron_variant, NMD_transcript_variant		1		ENSP00000482917

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

Gnomad4 AFR AF: 0.256

Gnomad4 AMR AF: 0.456

Gnomad4 ASJ AF: 0.442

Gnomad4 EAS AF: 0.507

Gnomad4 SAS AF: 0.410

Gnomad4 FIN AF: 0.424

Gnomad4 NFE AF: 0.453

Gnomad4 OTH AF: 0.398

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

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: rs9285254; hg19: chr13-66999815;