5-141182705-G-A

Variant names:

• chr5-141182705-G-A
• NM_020957.4:c.146G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_020957.4(PCDHB16):​c.146G>A​(p.Gly49Glu) 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. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PCDHB16 NM_020957.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.133
• Publications: 0 publications found

Genes affected

PCDHB16 (HGNC:14546): (protocadherin beta 16) 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):

ENSG00000279068 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10565263).
• BP6: Variant 5-141182705-G-A is Benign according to our data. Variant chr5-141182705-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3886517.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020957.4. 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
	PCDHB16	NM_020957.4	MANE Select	c.146G>A	p.Gly49Glu	missense	Exon 1 of 1	NP_066008.2	Q9NRJ7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCDHB16	ENST00000609684.3	TSL:6 MANE Select	c.146G>A	p.Gly49Glu	missense	Exon 1 of 1	ENSP00000477314.1	Q9NRJ7
	PCDHB16	ENST00000625044.1	TSL:2	c.-37+111G>A		intron	N/A	ENSP00000485449.1	A0A096LP81
	ENSG00000279068	ENST00000623407.1	TSL:4	n.186+111G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	11
DANN	Benign	0.90
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.096	N
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.97	T
PhyloP100		0.13
PrimateAI	Benign	0.42	T
Sift4G	Uncertain	0.0060	D
Vest4		0.14
MutPred		0.67		Gain of ubiquitination at K50 (P = 0.0918)
MVP		0.22
ClinPred		0.16	T
GERP RS		-2.9
PromoterAI		-0.024	Neutral
gMVP		0.69
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

hg19: chr5-140562280; COSMIC: COSV105002256; COSMIC: COSV105002256;