chr13-66631342-C-T

Position:

• chr13-66631342-C-T

Variant summary

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

The NM_203487.3(PCDH9):​c.3208G>A​(p.Asp1070Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PCDH9 NM_203487.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.53

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/exons	MANE	Protein	UniProt
PCDH9	NM_203487.3	c.3208G>A	p.Asp1070Asn	missense_variant	4/5	ENST00000377865.7	NP_982354.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCDH9	ENST00000377865.7	c.3208G>A	p.Asp1070Asn	missense_variant	4/5	1	NM_203487.3	ENSP00000367096.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 04, 2024

The c.3208G>A (p.D1070N) alteration is located in exon 4 (coding exon 3) of the PCDH9 gene. This alteration results from a G to A substitution at nucleotide position 3208, causing the aspartic acid (D) at amino acid position 1070 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.035	T;.
Eigen	Uncertain	0.65
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Pathogenic	0.98	D;D
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.45	T;T
MetaSVM	Benign	-0.57	T
MutationAssessor	Benign	1.6	L;.
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-1.8	N;.
REVEL	Benign	0.19
Sift	Uncertain	0.022	D;.
Sift4G	Pathogenic	0.0	D;T
Polyphen		0.93	P;D
Vest4		0.53
MutPred		0.37		Gain of catalytic residue at D1070 (P = 0);.;
MVP		0.66
MPC		0.39
ClinPred		0.92	D
GERP RS		5.6
Varity_R		0.11
gMVP		0.44

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-67205474;