chr5-141857305-T-C
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_032420.5(PCDH1):āc.3266A>Gā(p.Tyr1089Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,664 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.0000014 ( 0 hom. )
Consequence
PCDH1
NM_032420.5 missense
NM_032420.5 missense
Scores
9
4
4
Clinical Significance
Conservation
PhyloP100: 7.67
Genes affected
PCDH1 (HGNC:8655): (protocadherin 1) This gene belongs to the protocadherin subfamily within the cadherin superfamily. The encoded protein is a membrane protein found at cell-cell boundaries. It is involved in neural cell adhesion, suggesting a possible role in neuronal development. The protein includes an extracelllular region, containing 7 cadherin-like domains, a transmembrane region and a C-terminal cytoplasmic region. Cells expressing the protein showed cell aggregation activity. Alternative splicing occurs in this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.79
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PCDH1 | NM_032420.5 | c.3266A>G | p.Tyr1089Cys | missense_variant | 4/5 | ENST00000287008.8 | NP_115796.2 | |
PCDH1 | XM_005268452.4 | c.3314A>G | p.Tyr1105Cys | missense_variant | 4/5 | XP_005268509.2 | ||
PCDH1 | XM_005268454.6 | c.3314A>G | p.Tyr1105Cys | missense_variant | 4/6 | XP_005268511.2 | ||
PCDH1 | XM_017009517.3 | c.2129A>G | p.Tyr710Cys | missense_variant | 3/4 | XP_016865006.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PCDH1 | ENST00000287008.8 | c.3266A>G | p.Tyr1089Cys | missense_variant | 4/5 | 5 | NM_032420.5 | ENSP00000287008.3 | ||
PCDH1 | ENST00000503492.5 | c.1070A>G | p.Tyr357Cys | missense_variant | 3/5 | 5 | ENSP00000424667.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
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32
GnomAD3 exomes AF: 0.00000801 AC: 2AN: 249784Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135008
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1460664Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 726590
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GnomAD4 genome Cov.: 32
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32
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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 | Aug 02, 2023 | The c.3266A>G (p.Y1089C) alteration is located in exon 4 (coding exon 4) of the PCDH1 gene. This alteration results from a A to G substitution at nucleotide position 3266, causing the tyrosine (Y) at amino acid position 1089 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
.;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
T
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;N
REVEL
Uncertain
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;.
Vest4
MutPred
Loss of phosphorylation at Y1089 (P = 0.0034);.;
MVP
MPC
ClinPred
D
GERP RS
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