NM_203487.3:c.3037-159032C>A

Variant names:

• chr13-67062637-G-T
• rs4142274
• NM_203487.3:c.3037-159032C>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.3037-159032C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 152,074 control chromosomes in the GnomAD database, including 4,170 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 0.22 (4170 hom., cov: 32)
• Consequence: PCDH9 NM_203487.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.169
• Publications: 7 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCDH9	NM_203487.3	c.3037-159032C>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.3037-159032C>A		intron_variant	Intron 2 of 4	1	NM_203487.3	ENSP00000367096.2
PCDH9	ENST00000544246.5	c.3036+162768C>A		intron_variant	Intron 2 of 3	1		ENSP00000442186.2
PCDH9	ENST00000456367.5	c.3037-159032C>A		intron_variant	Intron 2 of 4	1		ENSP00000401699.2

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33568 AN: 151956 Hom.: 4160 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.563

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.221 AC: 33589 AN: 152074 Hom.: 4170 Cov.: 32 AF XY: 0.222 AC XY: 16511 AN XY: 74342

African (AFR) AF: 0.158 AC: 6551 AN: 41518

American (AMR) AF: 0.171 AC: 2608 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 813 AN: 3470

East Asian (EAS) AF: 0.563 AC: 2907 AN: 5160

South Asian (SAS) AF: 0.273 AC: 1316 AN: 4816

European-Finnish (FIN) AF: 0.200 AC: 2116 AN: 10574

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.245 AC: 16670 AN: 67954

Other (OTH) AF: 0.214 AC: 451 AN: 2110

Alfa AF: 0.238 Hom.: 19019

Bravo AF: 0.216

Asia WGS AF: 0.361 AC: 1251 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.6
DANN	Benign	0.70
PhyloP100		0.17
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: rs4142274; hg19: chr13-67636769;