rs149158184

Variant names:

• chr13-66304742-G-T
• rs149158184
• NM_203487.3:c.3627C>A

Your query was ambiguous. Multiple possible variants found:

• chr13-66304742-G-T
• chr13-66304742-G-A
• chr13-66304742-G-C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_203487.3(PCDH9):​c.3627C>A​(p.Ser1209Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00308 in 1,612,976 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0027 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0031 (22 hom.)
• Consequence: PCDH9 NM_203487.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.21
• Publications: 3 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-AS1 (HGNC:39897): (PCDH9 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004679233).
• BP6: Variant 13-66304742-G-T is Benign according to our data. Variant chr13-66304742-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2643836.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 406 AD gene.

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.3627C>A	p.Ser1209Arg	missense	Exon 5 of 5	NP_982354.1	X5D7N0
	PCDH9	NM_020403.5		c.3525C>A	p.Ser1175Arg	missense	Exon 4 of 4	NP_065136.1	Q9HC56-2
	PCDH9	NM_001318372.2		c.3501C>A	p.Ser1167Arg	missense	Exon 5 of 5	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.3627C>A	p.Ser1209Arg	missense	Exon 5 of 5	ENSP00000367096.2	Q9HC56-1
	PCDH9	ENST00000544246.5	TSL:1	c.3525C>A	p.Ser1175Arg	missense	Exon 4 of 4	ENSP00000442186.2	Q9HC56-2
	PCDH9	ENST00000456367.5	TSL:1	c.3501C>A	p.Ser1167Arg	missense	Exon 5 of 5	ENSP00000401699.2	B7ZM79

Frequencies

GnomAD3 genomes AF: 0.00268 AC: 407 AN: 151986 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000459

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00190

Gnomad ASJ AF: 0.0147

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00874

Gnomad FIN AF: 0.000661

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00357

Gnomad OTH AF: 0.00574

GnomAD2 exomes AF: 0.00403 AC: 1008 AN: 250428 AF XY: 0.00446

Gnomad AFR exome AF: 0.000554

Gnomad AMR exome AF: 0.00235

Gnomad ASJ exome AF: 0.0178

Gnomad EAS exome AF: 0.0000545

Gnomad FIN exome AF: 0.000418

Gnomad NFE exome AF: 0.00388

Gnomad OTH exome AF: 0.00378

GnomAD4 exome AF: 0.00312 AC: 4560 AN: 1460872 Hom.: 22 Cov.: 31 AF XY: 0.00341 AC XY: 2481 AN XY: 726784

African (AFR) AF: 0.000299 AC: 10 AN: 33442

American (AMR) AF: 0.00265 AC: 118 AN: 44610

Ashkenazi Jewish (ASJ) AF: 0.0169 AC: 441 AN: 26112

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39686

South Asian (SAS) AF: 0.00830 AC: 716 AN: 86232

European-Finnish (FIN) AF: 0.000619 AC: 33 AN: 53340

Middle Eastern (MID) AF: 0.00642 AC: 37 AN: 5764

European-Non Finnish (NFE) AF: 0.00267 AC: 2971 AN: 1111346

Other (OTH) AF: 0.00384 AC: 232 AN: 60340

GnomAD4 genome AF: 0.00267 AC: 406 AN: 152104 Hom.: 1 Cov.: 32 AF XY: 0.00272 AC XY: 202 AN XY: 74344

African (AFR) AF: 0.000458 AC: 19 AN: 41516

American (AMR) AF: 0.00190 AC: 29 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.0147 AC: 51 AN: 3466

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5166

South Asian (SAS) AF: 0.00853 AC: 41 AN: 4804

European-Finnish (FIN) AF: 0.000661 AC: 7 AN: 10592

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00357 AC: 243 AN: 67990

Other (OTH) AF: 0.00568 AC: 12 AN: 2112

Alfa AF: 0.00393 Hom.: 6

Bravo AF: 0.00243

TwinsUK AF: 0.00216 AC: 8

ALSPAC AF: 0.00311 AC: 12

ESP6500AA AF: 0.00113 AC: 5

ESP6500EA AF: 0.00256 AC: 22

ExAC AF: 0.00400 AC: 485

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.00453

EpiControl AF: 0.00380

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.079
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.0047	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		2.2
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.067
Sift	Benign	0.036	D
Sift4G	Benign	0.076	T
Polyphen		0.013	B
Vest4		0.33
MutPred		0.32		Gain of catalytic residue at D1213 (P = 0.0028)
MVP		0.18
MPC		0.34
ClinPred		0.014	T
GERP RS		4.0
Varity_R		0.10
gMVP		0.43
Mutation Taster		=100/0	polymorphism

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: rs149158184; hg19: chr13-66878874;