rs1334398

Variant names:

• chr13-66356467-T-C
• rs1334398
• NM_203487.3:c.3341-51439A>G

Variant summary

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

The NM_203487.3(PCDH9):​c.3341-51439A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 151,954 control chromosomes in the GnomAD database, including 14,222 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 0.41 (14222 hom., cov: 32)
• Consequence: PCDH9 NM_203487.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.408
• Publications: 2 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCDH9	NM_203487.3	c.3341-51439A>G		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.3341-51439A>G		intron_variant	Intron 4 of 4	1	NM_203487.3	ENSP00000367096.2
PCDH9	ENST00000544246.5	c.3239-51439A>G		intron_variant	Intron 3 of 3	1		ENSP00000442186.2
PCDH9	ENST00000456367.5	c.3215-51439A>G		intron_variant	Intron 4 of 4	1		ENSP00000401699.2
PCDH9	ENST00000614931.1	n.*254-51439A>G		intron_variant	Intron 3 of 3	1		ENSP00000482917.1

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61682 AN: 151836 Hom.: 14225 Cov.: 32

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.428

Gnomad SAS AF: 0.497

Gnomad FIN AF: 0.482

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.422

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

GnomAD4 genome AF: 0.406 AC: 61698 AN: 151954 Hom.: 14222 Cov.: 32 AF XY: 0.409 AC XY: 30369 AN XY: 74258

African (AFR) AF: 0.172 AC: 7157 AN: 41504

American (AMR) AF: 0.578 AC: 8801 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 1754 AN: 3470

East Asian (EAS) AF: 0.429 AC: 2210 AN: 5154

South Asian (SAS) AF: 0.497 AC: 2394 AN: 4820

European-Finnish (FIN) AF: 0.482 AC: 5090 AN: 10552

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.483 AC: 32764 AN: 67902

Other (OTH) AF: 0.421 AC: 888 AN: 2110

Alfa AF: 0.467 Hom.: 27111

Bravo AF: 0.404

Asia WGS AF: 0.424 AC: 1474 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.1
DANN	Benign	0.49
PhyloP100		-0.41
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: rs1334398; hg19: chr13-66930599;