GeneBe

rs3756323

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_018931.3(PCDHB11):​c.11A>C​(p.Gln4Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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. Q4R) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Consequence

PCDHB11
NM_018931.3 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.578
Variant links:
Genes affected
PCDHB11 (HGNC:8682): (protocadherin beta 11) This gene is a member of the protocadherin beta gene cluster, one of three related gene clusters tandemly linked on chromosome five. The gene clusters demonstrate an unusual genomic organization similar to that of B-cell and T-cell receptor gene clusters. The beta cluster contains 16 genes and 3 pseudogenes, each encoding 6 extracellular cadherin domains and a cytoplasmic tail that deviates from others in the cadherin superfamily. The extracellular domains interact in a homophilic manner to specify differential cell-cell connections. Unlike the alpha and gamma clusters, the transcripts from these genes are made up of only one large exon, not sharing common 3' exons as expected. These neural cadherin-like cell adhesion proteins are integral plasma membrane proteins. Their specific functions are unknown but they most likely play a critical role in the establishment and function of specific cell-cell neural connections. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.0559448).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PCDHB11NM_018931.3 linkc.11A>C p.Gln4Pro missense_variant Exon 1 of 1 ENST00000354757.5 NP_061754.1 Q9Y5F2-1
PCDHB@ n.141199785A>C intragenic_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PCDHB11ENST00000354757.5 linkc.11A>C p.Gln4Pro missense_variant Exon 1 of 1 6 NM_018931.3 ENSP00000346802.3 Q9Y5F2-1
PCDHB11ENST00000624887 linkc.-388A>C 5_prime_UTR_variant Exon 1 of 2 2 ENSP00000485553.1 Q9Y5F2-2
ENSG00000280029ENST00000624192.1 linkn.72+41888T>G intron_variant Intron 1 of 1 5
ENSG00000278936ENST00000624549.1 linkn.131+1481T>G intron_variant Intron 1 of 1 4

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.066
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.68
CADD
Benign
7.8
DANN
Benign
0.37
DEOGEN2
Benign
0.019
T
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.020
N
LIST_S2
Benign
0.14
T
M_CAP
Benign
0.0061
T
MetaRNN
Benign
0.056
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.20
N
PrimateAI
Benign
0.28
T
PROVEAN
Benign
-1.1
N
REVEL
Benign
0.023
Sift
Benign
0.28
T
Sift4G
Benign
0.28
T
Polyphen
0.0
B
Vest4
0.065
MutPred
0.26
Gain of glycosylation at Q4 (P = 0.0182);
MVP
0.24
MPC
0.28
ClinPred
0.029
T
GERP RS
0.24
Varity_R
0.089
gMVP
0.28

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: chr5-140579358; API