rs9540995

Variant names:

• chr13-67093848-C-A
• rs9540995
• NM_203487.3:c.3036+131557G>T

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+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
• 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=-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 rank	MANE	Protein	UniProt
PCDH9	NM_203487.3	c.3036+131557G>T		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+131557G>T		intron_variant	Intron 2 of 4	1	NM_203487.3	ENSP00000367096.2
PCDH9	ENST00000544246.5	c.3036+131557G>T		intron_variant	Intron 2 of 3	1		ENSP00000442186.2
PCDH9	ENST00000456367.5	c.3036+131557G>T		intron_variant	Intron 2 of 4	1		ENSP00000401699.2

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

African (AFR) AF: 0.0941 AC: 3899 AN: 41432

American (AMR) AF: 0.0851 AC: 1297 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.0285 AC: 99 AN: 3468

East Asian (EAS) AF: 0.0252 AC: 130 AN: 5158

South Asian (SAS) AF: 0.0453 AC: 218 AN: 4812

European-Finnish (FIN) AF: 0.103 AC: 1086 AN: 10550

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.119 AC: 8096 AN: 67960

Other (OTH) AF: 0.0873 AC: 184 AN: 2108

Alfa AF: 0.102 Hom.: 133

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
PhyloP100		-0.038
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: rs9540995; hg19: chr13-67667980;