rs1036995

Variant names:

• chr13-66436686-C-T
• rs1036995
• NM_203487.3:c.3341-131658G>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.3341-131658G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 151,826 control chromosomes in the GnomAD database, including 12,606 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 0.40 (12606 hom., cov: 30)
• Consequence: PCDH9 NM_203487.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.89
• Publications: 9 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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCDH9	NM_203487.3	c.3341-131658G>A		intron_variant	Intron 4 of 4	ENST00000377865.7	NP_982354.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCDH9	ENST00000377865.7	c.3341-131658G>A		intron_variant	Intron 4 of 4	1	NM_203487.3	ENSP00000367096.2
PCDH9	ENST00000544246.5	c.3239-131658G>A		intron_variant	Intron 3 of 3	1		ENSP00000442186.2
PCDH9	ENST00000456367.5	c.3215-131658G>A		intron_variant	Intron 4 of 4	1		ENSP00000401699.2
PCDH9	ENST00000614931.1	n.*254-131658G>A		intron_variant	Intron 3 of 3	1		ENSP00000482917.1

Frequencies

GnomAD3 genomes AF: 0.396 AC: 60115 AN: 151708 Hom.: 12600 Cov.: 30

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.360

Gnomad SAS AF: 0.529

Gnomad FIN AF: 0.528

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.452

Gnomad OTH AF: 0.403

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

GnomAD4 genome AF: 0.396 AC: 60159 AN: 151826 Hom.: 12606 Cov.: 30 AF XY: 0.402 AC XY: 29816 AN XY: 74172

African (AFR) AF: 0.250 AC: 10344 AN: 41400

American (AMR) AF: 0.408 AC: 6227 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.422 AC: 1463 AN: 3470

East Asian (EAS) AF: 0.360 AC: 1855 AN: 5150

South Asian (SAS) AF: 0.530 AC: 2551 AN: 4812

European-Finnish (FIN) AF: 0.528 AC: 5553 AN: 10514

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.452 AC: 30711 AN: 67924

Other (OTH) AF: 0.405 AC: 854 AN: 2110

Alfa AF: 0.428 Hom.: 53513

Bravo AF: 0.375

Asia WGS AF: 0.437 AC: 1517 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.20
DANN	Benign	0.45
PhyloP100		-1.9
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: rs1036995; hg19: chr13-67010818;