5-140786313-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018900.4(PCDHA1):​c.23G>T​(p.Gly8Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,054 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PCDHA1
NM_018900.4 missense

Scores

1
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.505
Variant links:
Genes affected
PCDHA1 (HGNC:8663): (protocadherin alpha 1) This gene is a member of the protocadherin alpha gene cluster, one of three related gene clusters tandemly linked on chromosome five that demonstrate an unusual genomic organization similar to that of B-cell and T-cell receptor gene clusters. The alpha gene cluster is composed of 15 cadherin superfamily genes related to the mouse CNR genes and consists of 13 highly similar and 2 more distantly related coding sequences. The tandem array of 15 N-terminal exons, or variable exons, are followed by downstream C-terminal exons, or constant exons, which are shared by all genes in the cluster. The large, uninterrupted N-terminal exons each encode six cadherin ectodomains while the C-terminal exons encode the cytoplasmic domain. These neural cadherin-like cell adhesion proteins are integral plasma membrane proteins that most likely play a critical role in the establishment and function of specific cell-cell connections in the brain. Alternative splicing has been observed and additional variants have been suggested but their full-length nature has yet to be determined. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.19856852).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PCDHA1NM_018900.4 linkc.23G>T p.Gly8Val missense_variant Exon 1 of 4 ENST00000504120.4 NP_061723.1 Q9Y5I3-1
PCDHA1NM_031410.2 linkc.23G>T p.Gly8Val missense_variant Exon 1 of 1 NP_113598.1 Q9Y5I3-3
PCDHA1NM_031411.3 linkc.23G>T p.Gly8Val missense_variant Exon 1 of 4 NP_113599.1 Q9Y5I3-2
PCDHA@ n.140786313G>T intragenic_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PCDHA1ENST00000504120.4 linkc.23G>T p.Gly8Val missense_variant Exon 1 of 4 1 NM_018900.4 ENSP00000420840.3 Q9Y5I3-1
PCDHA1ENST00000394633.7 linkc.23G>T p.Gly8Val missense_variant Exon 1 of 4 1 ENSP00000378129.3 Q9Y5I3-2
PCDHA1ENST00000378133.4 linkc.23G>T p.Gly8Val missense_variant Exon 1 of 1 6 ENSP00000367373.3 Q9Y5I3-3
ENSG00000279726ENST00000655235.1 linkn.3199C>A non_coding_transcript_exon_variant Exon 2 of 2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1458054
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
725148
show subpopulations
Gnomad4 AFR exome
AF:
0.00
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:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.073
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.45
CADD
Benign
14
DANN
Benign
0.48
DEOGEN2
Benign
0.36
.;.;T
Eigen
Benign
-0.85
Eigen_PC
Benign
-0.97
FATHMM_MKL
Benign
0.16
N
LIST_S2
Benign
0.23
T;T;T
M_CAP
Benign
0.017
T
MetaRNN
Benign
0.20
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.5
L;L;L
PROVEAN
Uncertain
-2.9
D;D;D
REVEL
Benign
0.079
Sift
Benign
0.12
T;T;T
Sift4G
Benign
0.16
T;T;T
Polyphen
0.91
P;B;B
Vest4
0.38
MutPred
0.54
Loss of sheet (P = 0.0037);Loss of sheet (P = 0.0037);Loss of sheet (P = 0.0037);
MVP
0.65
MPC
0.65
ClinPred
0.60
D
GERP RS
0.49
Varity_R
0.081
gMVP
0.59

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: chr5-140165898; API