13-66913550-T-G

Variant names:

• chr13-66913550-T-G
• rs10492592
• NM_203487.3:c.3037-9945A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_203487.3(PCDH9):​c.3037-9945A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 151,946 control chromosomes in the GnomAD database, including 2,032 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 0.15 (2032 hom., cov: 32)
• Consequence: PCDH9 NM_203487.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.424
• Publications: 5 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]

PCDH9-AS2 (HGNC:39896): (PCDH9 antisense RNA 2)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.208 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCDH9	NM_203487.3	MANE Select	c.3037-9945A>C		intron	N/A	NP_982354.1	X5D7N0
	PCDH9	NM_020403.5		c.3037-282139A>C		intron	N/A	NP_065136.1	Q9HC56-2
	PCDH9	NM_001318372.2		c.3037-9945A>C		intron	N/A	NP_001305301.1	B7ZM79

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCDH9	ENST00000377865.7	TSL:1 MANE Select	c.3037-9945A>C		intron	N/A	ENSP00000367096.2	Q9HC56-1
	PCDH9	ENST00000544246.5	TSL:1	c.3037-282139A>C		intron	N/A	ENSP00000442186.2	Q9HC56-2
	PCDH9	ENST00000456367.5	TSL:1	c.3037-9945A>C		intron	N/A	ENSP00000401699.2	B7ZM79

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22625 AN: 151828 Hom.: 2031 Cov.: 32

Gnomad AFR AF: 0.0640

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.00580

Gnomad SAS AF: 0.0501

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.149 AC: 22627 AN: 151946 Hom.: 2032 Cov.: 32 AF XY: 0.144 AC XY: 10695 AN XY: 74264

African (AFR) AF: 0.0639 AC: 2650 AN: 41492

American (AMR) AF: 0.134 AC: 2045 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 859 AN: 3458

East Asian (EAS) AF: 0.00581 AC: 30 AN: 5164

South Asian (SAS) AF: 0.0508 AC: 245 AN: 4822

European-Finnish (FIN) AF: 0.189 AC: 1996 AN: 10574

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.211 AC: 14305 AN: 67914

Other (OTH) AF: 0.159 AC: 334 AN: 2106

Alfa AF: 0.185 Hom.: 5317

Bravo AF: 0.141

Asia WGS AF: 0.0330 AC: 115 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.0
DANN	Benign	0.72
PhyloP100		-0.42
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: rs10492592; hg19: chr13-67487682;