NM_018931.3:c.11A>C

Variant names:

• chr5-141199785-A-C
• NM_018931.3:c.11A>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.578

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]

PCDHB@ (HGNC:8679):

ENSG00000280029 (HGNC:):

ACMG classification

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
PCDHB11	NM_018931.3	c.11A>C	p.Gln4Pro	missense_variant	Exon 1 of 1	ENST00000354757.5	NP_061754.1
PCDHB@		n.141199785A>C		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCDHB11	ENST00000354757.5	c.11A>C	p.Gln4Pro	missense_variant	Exon 1 of 1	6	NM_018931.3	ENSP00000346802.3
PCDHB11	ENST00000624887	c.-388A>C		5_prime_UTR_variant	Exon 1 of 2	2		ENSP00000485553.1
ENSG00000280029	ENST00000624192.1	n.72+41888T>G		intron_variant	Intron 1 of 1	5
ENSG00000278936	ENST00000624549.1	n.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;