rs747718825

Variant names:

• chr13-66631404-C-A
• rs747718825
• NM_203487.3:c.3146G>T

Your query was ambiguous. Multiple possible variants found:

• chr13-66631404-C-A
• chr13-66631404-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_203487.3(PCDH9):​c.3146G>T​(p.Arg1049Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,449,612 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1049C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: PCDH9 NM_203487.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.57

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCDH9	NM_203487.3	c.3146G>T	p.Arg1049Leu	missense_variant	Exon 4 of 5	ENST00000377865.7	NP_982354.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCDH9	ENST00000377865.7	c.3146G>T	p.Arg1049Leu	missense_variant	Exon 4 of 5	1	NM_203487.3	ENSP00000367096.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250740 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135510

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000882

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000207 AC: 3 AN: 1449612 Hom.: 0 Cov.: 27 AF XY: 0.00000138 AC XY: 1 AN XY: 722054

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000272

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.24
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.055	T;.
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D;D
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.73	D;D
MetaSVM	Benign	-0.46	T
MutationAssessor	Benign	1.8	L;.
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-2.5	N;.
REVEL	Uncertain	0.46
Sift	Pathogenic	0.0	D;.
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.41	B;B
Vest4		0.92
MutPred		0.53		Gain of catalytic residue at E1046 (P = 0.0117);.;
MVP		0.83
MPC		0.41
ClinPred		0.96	D
GERP RS		5.6
Varity_R		0.30
gMVP		0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs747718825; hg19: chr13-67205536;