rs3764117

Variant names:

• chr13-66631388-A-G
• rs3764117
• NM_203487.3:c.3162T>C

Your query was ambiguous. Multiple possible variants found:

• chr13-66631388-A-G
• chr13-66631388-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_203487.3(PCDH9):​c.3162T>C​(p.His1054His) variant causes a synonymous change. The variant allele was found at a frequency of 0.00333 in 1,610,806 control chromosomes in the GnomAD database, including 193 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0042 (20 hom., cov: 32)
  • Exomes 𝑓: 0.0032 (173 hom.)
• Consequence: PCDH9 NM_203487.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.00
• 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]

LOC105370247 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 13-66631388-A-G is Benign according to our data. Variant chr13-66631388-A-G is described in ClinVar as Benign. ClinVar VariationId is 780154.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0743 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.3162T>C	p.His1054His	synonymous	Exon 4 of 5	NP_982354.1	X5D7N0
	PCDH9	NM_020403.5		c.3060T>C	p.His1020His	synonymous	Exon 3 of 4	NP_065136.1	Q9HC56-2
	PCDH9	NM_001318372.2		c.3139-103T>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.3162T>C	p.His1054His	synonymous	Exon 4 of 5	ENSP00000367096.2	Q9HC56-1
	PCDH9	ENST00000544246.5	TSL:1	c.3060T>C	p.His1020His	synonymous	Exon 3 of 4	ENSP00000442186.2	Q9HC56-2
	PCDH9	ENST00000456367.5	TSL:1	c.3139-103T>C		intron	N/A	ENSP00000401699.2	B7ZM79

Frequencies

GnomAD3 genomes AF: 0.00423 AC: 644 AN: 152166 Hom.: 20 Cov.: 32

Gnomad AFR AF: 0.000265

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00404

Gnomad EAS AF: 0.0814

Gnomad SAS AF: 0.00248

Gnomad FIN AF: 0.0147

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00806 AC: 2024 AN: 251240 AF XY: 0.00764

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00377

Gnomad EAS exome AF: 0.0846

Gnomad FIN exome AF: 0.0140

Gnomad NFE exome AF: 0.000405

Gnomad OTH exome AF: 0.00359

GnomAD4 exome AF: 0.00324 AC: 4730 AN: 1458522 Hom.: 173 Cov.: 28 AF XY: 0.00326 AC XY: 2364 AN XY: 725932

African (AFR) AF: 0.000209 AC: 7 AN: 33416

American (AMR) AF: 0.000179 AC: 8 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00341 AC: 89 AN: 26120

East Asian (EAS) AF: 0.0834 AC: 3308 AN: 39672

South Asian (SAS) AF: 0.00226 AC: 195 AN: 86184

European-Finnish (FIN) AF: 0.0127 AC: 676 AN: 53362

Middle Eastern (MID) AF: 0.000694 AC: 4 AN: 5764

European-Non Finnish (NFE) AF: 0.000157 AC: 174 AN: 1109006

Other (OTH) AF: 0.00446 AC: 269 AN: 60282

GnomAD4 genome AF: 0.00419 AC: 638 AN: 152284 Hom.: 20 Cov.: 32 AF XY: 0.00555 AC XY: 413 AN XY: 74456

African (AFR) AF: 0.000265 AC: 11 AN: 41564

American (AMR) AF: 0.000262 AC: 4 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00404 AC: 14 AN: 3468

East Asian (EAS) AF: 0.0807 AC: 418 AN: 5182

South Asian (SAS) AF: 0.00228 AC: 11 AN: 4830

European-Finnish (FIN) AF: 0.0147 AC: 156 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000294 AC: 20 AN: 68020

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.000731 Hom.: 2

Bravo AF: 0.00395

Asia WGS AF: 0.0260 AC: 92 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000119

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	7.9
DANN	Benign	0.70
PhyloP100		4.0
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3764117; hg19: chr13-67205520; COSMIC: COSV60536524; COSMIC: COSV60536524;