13-66646671-C-T

Position:

• chr13-66646671-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000377865.7(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 ENST00000377865.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCDH9	NM_203487.3	c.3139-15260G>A		intron_variant		ENST00000377865.7	NP_982354.1
LOC105370247	XR_007063818.1	n.169-13390C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCDH9	ENST00000377865.7	c.3139-15260G>A		intron_variant		1	NM_203487.3	ENSP00000367096
PCDH9	ENST00000456367.5	c.3139-15386G>A		intron_variant		1		ENSP00000401699
PCDH9	ENST00000544246.5	c.3037-15260G>A		intron_variant		1		ENSP00000442186	P1
PCDH9	ENST00000614931.1	c.*52-15260G>A		intron_variant, NMD_transcript_variant		1		ENSP00000482917

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

Gnomad4 AFR AF: 0.121

Gnomad4 AMR AF: 0.0305

Gnomad4 ASJ AF: 0.0170

Gnomad4 EAS AF: 0.0284

Gnomad4 SAS AF: 0.0313

Gnomad4 FIN AF: 0.0116

Gnomad4 NFE AF: 0.0181

Gnomad4 OTH AF: 0.0464

Alfa AF: 0.0237 Hom.: 64

Bravo AF: 0.0524

Asia WGS AF: 0.0380 AC: 130 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.80
DANN	Benign	0.23

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

Publications

LitVar

Other links and lift over

dbSNP: rs964381; hg19: chr13-67220803;