rs9540995

chr13-67093848-C-A

Variant summary

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

The NM_203487.3(PCDH9):c.3036+131557G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0995 in 151,942 control chromosomes in the GnomAD database, including 817 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 0.10 (817 hom., cov: 32)
• Consequence: PCDH9 NM_203487.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0380

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCDH9	NM_203487.3	c.3036+131557G>T		intron_variant		ENST00000377865.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCDH9	ENST00000377865.7	c.3036+131557G>T		intron_variant		1	NM_203487.3
PCDH9	ENST00000456367.5	c.3036+131557G>T		intron_variant		1
PCDH9	ENST00000544246.5	c.3036+131557G>T		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.0995 AC: 15108 AN: 151824 Hom.: 813 Cov.: 32

Gnomad AFR AF: 0.0943

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.0851

Gnomad ASJ AF: 0.0285

Gnomad EAS AF: 0.0255

Gnomad SAS AF: 0.0451

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.0839

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

GnomAD4 genome AF: 0.0995 AC: 15120 AN: 151942 Hom.: 817 Cov.: 32 AF XY: 0.0963 AC XY: 7152 AN XY: 74254

Gnomad4 AFR AF: 0.0941

Gnomad4 AMR AF: 0.0851

Gnomad4 ASJ AF: 0.0285

Gnomad4 EAS AF: 0.0252

Gnomad4 SAS AF: 0.0453

Gnomad4 FIN AF: 0.103

Gnomad4 NFE AF: 0.119

Gnomad4 OTH AF: 0.0873

Alfa AF: 0.102 Hom.: 131

Bravo AF: 0.100

Asia WGS AF: 0.0750 AC: 262 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.8
Dann	Benign	0.35

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: rs9540995; hg19: chr13-67667980;