13-66646671-C-T

Variant names:

• chr13-66646671-C-T
• rs964381
• NM_203487.3:c.3139-15260G>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.3139-15260G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.048 in 152,160 control chromosomes in the GnomAD database, including 339 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 0.048 (339 hom., cov: 32)
• Consequence: PCDH9 NM_203487.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26
• 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]

LOC105370247 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203487.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCDH9	NM_203487.3	MANE Select	c.3139-15260G>A		intron	N/A	NP_982354.1
	PCDH9	NM_020403.5		c.3037-15260G>A		intron	N/A	NP_065136.1
	PCDH9	NM_001318372.2		c.3139-15386G>A		intron	N/A	NP_001305301.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCDH9	ENST00000377865.7	TSL:1 MANE Select	c.3139-15260G>A		intron	N/A	ENSP00000367096.2
	PCDH9	ENST00000544246.5	TSL:1	c.3037-15260G>A		intron	N/A	ENSP00000442186.2
	PCDH9	ENST00000456367.5	TSL:1	c.3139-15386G>A		intron	N/A	ENSP00000401699.2

Frequencies

GnomAD3 genomes AF: 0.0478 AC: 7273 AN: 152042 Hom.: 335 Cov.: 32

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0306

Gnomad ASJ AF: 0.0170

Gnomad EAS AF: 0.0283

Gnomad SAS AF: 0.0315

Gnomad FIN AF: 0.0116

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0181

Gnomad OTH AF: 0.0464

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

GnomAD4 genome AF: 0.0480 AC: 7300 AN: 152160 Hom.: 339 Cov.: 32 AF XY: 0.0471 AC XY: 3504 AN XY: 74408

African (AFR) AF: 0.121 AC: 5011 AN: 41486

American (AMR) AF: 0.0305 AC: 466 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0170 AC: 59 AN: 3470

East Asian (EAS) AF: 0.0284 AC: 147 AN: 5180

South Asian (SAS) AF: 0.0313 AC: 151 AN: 4822

European-Finnish (FIN) AF: 0.0116 AC: 123 AN: 10592

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0181 AC: 1234 AN: 68004

Other (OTH) AF: 0.0464 AC: 98 AN: 2112

Alfa AF: 0.0250 Hom.: 94

Bravo AF: 0.0524

Asia WGS AF: 0.0380 AC: 130 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.80
DANN	Benign	0.23
PhyloP100		-1.3
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: rs964381; hg19: chr13-67220803;