rs935822454

Variant names:

• chr4-133150628-C-A
• NM_032961.3:c.488C>A

Your query was ambiguous. Multiple possible variants found:

• chr4-133150628-C-A
• chr4-133150628-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032961.3(PCDH10):​c.488C>A​(p.Pro163His) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,340 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. P163L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PCDH10 NM_032961.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.82

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36488372).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCDH10	NM_032961.3	c.488C>A	p.Pro163His	missense_variant	Exon 1 of 5	ENST00000264360.7	NP_116586.1
PCDH10	NM_020815.3	c.488C>A	p.Pro163His	missense_variant	Exon 1 of 1		NP_065866.1
PCDH10	XM_011532150.2	c.488C>A	p.Pro163His	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.488C>A	p.Pro163His	missense_variant	Exon 1 of 5	1	NM_032961.3	ENSP00000264360.4
PCDH10	ENST00000618019.1	c.488C>A	p.Pro163His	missense_variant	Exon 1 of 1	6		ENSP00000480512.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461340 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 727000

Gnomad4 AFR exome AF: 0.0000597

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.45	.;T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.69	T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.36	T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.2	M;M
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-4.0	.;D
REVEL	Benign	0.18
Sift	Uncertain	0.014	.;D
Sift4G	Benign	0.080	T;T
Polyphen		0.88	.;P
Vest4		0.46
MutPred		0.44		Loss of catalytic residue at P163 (P = 0.02);Loss of catalytic residue at P163 (P = 0.02);
MVP		0.29
ClinPred		0.99	D
GERP RS		4.8
Varity_R		0.63
gMVP		0.39

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: chr4-134071783;