13-66953112-T-C

Variant names:

• chr13-66953112-T-C
• rs1028730
• NM_203487.3:c.3037-49507A>G

Variant summary

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

The NM_203487.3(PCDH9):​c.3037-49507A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 151,952 control chromosomes in the GnomAD database, including 7,230 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 0.30 (7230 hom., cov: 32)
• Consequence: PCDH9 NM_203487.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.47
• Publications: 6 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.609 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.3037-49507A>G		intron	N/A	NP_982354.1	X5D7N0
	PCDH9	NM_020403.5		c.3036+272293A>G		intron	N/A	NP_065136.1	Q9HC56-2
	PCDH9	NM_001318372.2		c.3037-49507A>G		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.3037-49507A>G		intron	N/A	ENSP00000367096.2	Q9HC56-1
	PCDH9	ENST00000544246.5	TSL:1	c.3036+272293A>G		intron	N/A	ENSP00000442186.2	Q9HC56-2
	PCDH9	ENST00000456367.5	TSL:1	c.3037-49507A>G		intron	N/A	ENSP00000401699.2	B7ZM79

Frequencies

GnomAD3 genomes AF: 0.296 AC: 44962 AN: 151838 Hom.: 7218 Cov.: 32

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.377

Gnomad EAS AF: 0.627

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.309

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

GnomAD4 genome AF: 0.296 AC: 44986 AN: 151952 Hom.: 7230 Cov.: 32 AF XY: 0.298 AC XY: 22128 AN XY: 74240

African (AFR) AF: 0.204 AC: 8456 AN: 41438

American (AMR) AF: 0.340 AC: 5191 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.377 AC: 1307 AN: 3468

East Asian (EAS) AF: 0.627 AC: 3239 AN: 5162

South Asian (SAS) AF: 0.279 AC: 1341 AN: 4806

European-Finnish (FIN) AF: 0.308 AC: 3253 AN: 10548

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.313 AC: 21241 AN: 67960

Other (OTH) AF: 0.313 AC: 660 AN: 2112

Alfa AF: 0.314 Hom.: 8438

Bravo AF: 0.300

Asia WGS AF: 0.388 AC: 1352 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.11
DANN	Benign	0.67
PhyloP100		-2.5
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: rs1028730; hg19: chr13-67527244;