4-133150669-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_032961.3(PCDH10):c.529G>A(p.Gly177Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,613,160 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 30)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
PCDH10
NM_032961.3 missense
NM_032961.3 missense
Scores
2
12
5
Clinical Significance
Conservation
PhyloP100: 9.99
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]
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ACMG classification
Classification made for transcript
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 |
---|---|---|---|---|---|---|---|---|
PCDH10 | NM_032961.3 | c.529G>A | p.Gly177Ser | missense_variant | 1/5 | ENST00000264360.7 | NP_116586.1 | |
PCDH10 | NM_020815.3 | c.529G>A | p.Gly177Ser | missense_variant | 1/1 | NP_065866.1 | ||
PCDH10 | XM_011532150.2 | c.529G>A | p.Gly177Ser | missense_variant | 1/5 | XP_011530452.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PCDH10 | ENST00000264360.7 | c.529G>A | p.Gly177Ser | missense_variant | 1/5 | 1 | NM_032961.3 | ENSP00000264360.4 | ||
PCDH10 | ENST00000618019.1 | c.529G>A | p.Gly177Ser | missense_variant | 1/1 | 6 | ENSP00000480512.1 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 151868Hom.: 0 Cov.: 30
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GnomAD3 exomes AF: 0.0000120 AC: 3AN: 249718Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135444
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GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461174Hom.: 0 Cov.: 36 AF XY: 0.00000138 AC XY: 1AN XY: 726932
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GnomAD4 genome AF: 0.00000658 AC: 1AN: 151986Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 74276
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 25, 2023 | The c.529G>A (p.G177S) alteration is located in exon 1 (coding exon 1) of the PCDH10 gene. This alteration results from a G to A substitution at nucleotide position 529, causing the glycine (G) at amino acid position 177 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Uncertain
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
.;D
REVEL
Uncertain
Sift
Uncertain
.;D
Sift4G
Benign
T;T
Polyphen
1.0
.;D
Vest4
MutPred
Gain of sheet (P = 0.0266);Gain of sheet (P = 0.0266);
MVP
ClinPred
D
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at