rs9529180

Variant names:

• chr13-67072431-C-T
• rs9529180
• NM_203487.3:c.3036+152974G>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.3036+152974G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,132 control chromosomes in the GnomAD database, including 998 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 0.11 (998 hom., cov: 32)
• Consequence: PCDH9 NM_203487.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02
• 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCDH9	NM_203487.3	c.3036+152974G>A		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+152974G>A		intron_variant	Intron 2 of 4	1	NM_203487.3	ENSP00000367096.2
PCDH9	ENST00000544246.5	c.3036+152974G>A		intron_variant	Intron 2 of 3	1		ENSP00000442186.2
PCDH9	ENST00000456367.5	c.3036+152974G>A		intron_variant	Intron 2 of 4	1		ENSP00000401699.2

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16658 AN: 152014 Hom.: 993 Cov.: 32

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.0894

Gnomad ASJ AF: 0.0288

Gnomad EAS AF: 0.0254

Gnomad SAS AF: 0.0472

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.0940

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

GnomAD4 genome AF: 0.110 AC: 16682 AN: 152132 Hom.: 998 Cov.: 32 AF XY: 0.106 AC XY: 7908 AN XY: 74364

African (AFR) AF: 0.129 AC: 5339 AN: 41496

American (AMR) AF: 0.0893 AC: 1363 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.0288 AC: 100 AN: 3472

East Asian (EAS) AF: 0.0251 AC: 130 AN: 5180

South Asian (SAS) AF: 0.0472 AC: 228 AN: 4826

European-Finnish (FIN) AF: 0.103 AC: 1092 AN: 10598

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.119 AC: 8114 AN: 67988

Other (OTH) AF: 0.0973 AC: 205 AN: 2106

Alfa AF: 0.111 Hom.: 1678

Bravo AF: 0.111

Asia WGS AF: 0.0790 AC: 276 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.48
PhyloP100		-1.0
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: rs9529180; hg19: chr13-67646563;