4-133150609-C-G

Variant names:

• chr4-133150609-C-G
• rs746677791
• NM_032961.3:c.469C>G

Variant summary

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

The NM_032961.3(PCDH10):​c.469C>G​(p.Arg157Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. R157S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 30)
• Consequence: PCDH10 NM_032961.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.96

Genes affected

PCDH10 (HGNC:13404): (protocadherin 10) This gene belongs to the protocadherin gene family, a subfamily of the cadherin superfamily. This family member contains 6 extracellular cadherin domains, a transmembrane domain and a cytoplasmic tail differing from those of the classical cadherins. The encoded protein is a cadherin-related neuronal receptor thought to function in the establishment of specific cell-cell connections in the brain. This gene plays a role in inhibiting cancer cell motility and cell migration. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2015]

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
PCDH10	NM_032961.3	c.469C>G	p.Arg157Gly	missense_variant	Exon 1 of 5	ENST00000264360.7	NP_116586.1
PCDH10	NM_020815.3	c.469C>G	p.Arg157Gly	missense_variant	Exon 1 of 1		NP_065866.1
PCDH10	XM_011532150.2	c.469C>G	p.Arg157Gly	missense_variant	Exon 1 of 5		XP_011530452.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCDH10	ENST00000264360.7	c.469C>G	p.Arg157Gly	missense_variant	Exon 1 of 5	1	NM_032961.3	ENSP00000264360.4
PCDH10	ENST00000618019.1	c.469C>G	p.Arg157Gly	missense_variant	Exon 1 of 1	6		ENSP00000480512.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.49	.;T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.84	T;D
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.72	D;D
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.9	L;L
PrimateAI	Uncertain	0.77	T
PROVEAN	Pathogenic	-4.8	.;D
REVEL	Benign	0.25
Sift	Uncertain	0.011	.;D
Sift4G	Uncertain	0.048	D;D
Polyphen		0.56	.;P
Vest4		0.66
MutPred		0.45		Loss of catalytic residue at R157 (P = 0.063);Loss of catalytic residue at R157 (P = 0.063);
MVP		0.90
ClinPred		0.99	D
GERP RS		3.9
Varity_R		0.66
gMVP		0.78

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

LitVar

Other links and lift over

dbSNP: rs746677791; hg19: chr4-134071764;