rs17081231

Variant names:

• chr13-66393490-A-G
• rs17081231
• NM_203487.3:c.3341-88462T>C

Variant summary

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

The NM_203487.3(PCDH9):​c.3341-88462T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0297 in 152,252 control chromosomes in the GnomAD database, including 178 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 0.030 (178 hom., cov: 32)
• Consequence: PCDH9 NM_203487.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.73
• Publications: 11 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 (EAS) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCDH9	NM_203487.3	c.3341-88462T>C		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.3341-88462T>C		intron_variant	Intron 4 of 4	1	NM_203487.3	ENSP00000367096.2
PCDH9	ENST00000544246.5	c.3239-88462T>C		intron_variant	Intron 3 of 3	1		ENSP00000442186.2
PCDH9	ENST00000456367.5	c.3215-88462T>C		intron_variant	Intron 4 of 4	1		ENSP00000401699.2
PCDH9	ENST00000614931.1	n.*254-88462T>C		intron_variant	Intron 3 of 3	1		ENSP00000482917.1

Frequencies

GnomAD3 genomes AF: 0.0297 AC: 4517 AN: 152134 Hom.: 175 Cov.: 32

Gnomad AFR AF: 0.00524

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0241

Gnomad ASJ AF: 0.0389

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.0993

Gnomad FIN AF: 0.0732

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0215

Gnomad OTH AF: 0.0296

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

GnomAD4 genome AF: 0.0297 AC: 4528 AN: 152252 Hom.: 178 Cov.: 32 AF XY: 0.0340 AC XY: 2532 AN XY: 74438

African (AFR) AF: 0.00522 AC: 217 AN: 41554

American (AMR) AF: 0.0240 AC: 367 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0389 AC: 135 AN: 3470

East Asian (EAS) AF: 0.190 AC: 981 AN: 5174

South Asian (SAS) AF: 0.0985 AC: 475 AN: 4822

European-Finnish (FIN) AF: 0.0732 AC: 776 AN: 10600

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0216 AC: 1466 AN: 68024

Other (OTH) AF: 0.0364 AC: 77 AN: 2114

Alfa AF: 0.0281 Hom.: 658

Bravo AF: 0.0249

Asia WGS AF: 0.165 AC: 570 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	10
DANN	Benign	0.83
PhyloP100		1.7
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: rs17081231; hg19: chr13-66967622;