NM_018932.4:c.32T>G

Variant names:

• chr5-141208939-T-G
• rs549056314
• NM_018932.4:c.32T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018932.4(PCDHB12):​c.32T>G​(p.Ile11Arg) 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. 16/22 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. I11T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PCDHB12 NM_018932.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.255
• Publications: 1 publications found

Genes affected

PCDHB12 (HGNC:8683): (protocadherin beta 12) 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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.085745126).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018932.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCDHB12	NM_018932.4	MANE Select	c.32T>G	p.Ile11Arg	missense	Exon 1 of 1	NP_061755.1	Q9Y5F1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCDHB12	ENST00000239450.4	TSL:6 MANE Select	c.32T>G	p.Ile11Arg	missense	Exon 1 of 1	ENSP00000239450.2	Q9Y5F1-1
	PCDHB12	ENST00000622978.1	TSL:2	c.32T>G	p.Ile11Arg	missense	Exon 1 of 2	ENSP00000485352.1	A0A096LP27
	PCDHB12	ENST00000624949.1	TSL:2	c.-102T>G		5_prime_UTR	Exon 1 of 2	ENSP00000485303.1	Q9Y5F1-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	15
DANN	Benign	0.90
DEOGEN2	Benign	0.00040	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.027	T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.086	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.050	N
PhyloP100		-0.26
PrimateAI	Benign	0.38	T
PROVEAN	Benign	2.7	N
REVEL	Benign	0.066
Sift	Benign	0.37	T
Sift4G	Benign	0.11	T
Polyphen		0.0010	B
Vest4		0.33
MutPred		0.54		Gain of disorder (P = 0.0291)
MVP		0.23
MPC		0.34
ClinPred		0.034	T
GERP RS		-2.0
PromoterAI		-0.0087	Neutral
Varity_R		0.051
gMVP		0.44
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs549056314; hg19: chr5-140588511;