chr5-140452-C-G

Variant names:

• chr5-140452-C-G
• rs1033372982
• NM_052909.5:c.1213C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_052909.5(PLEKHG4B):​c.1213C>G​(p.Arg405Gly) 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. R405W) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PLEKHG4B NM_052909.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.47
• Publications: 0 publications found

Genes affected

PLEKHG4B (HGNC:29399): (pleckstrin homology and RhoGEF domain containing G4B) This gene encodes a large protein that contains a pleckstrin homology domain and may function as a guanine nucleotide exchange factor. [provided by RefSeq, May 2017]

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=0.04678297).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052909.5. 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
	PLEKHG4B	NM_052909.5	MANE Select	c.1213C>G	p.Arg405Gly	missense	Exon 3 of 20	NP_443141.4	Q96PX9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLEKHG4B	ENST00000637938.2	TSL:5 MANE Select	c.1213C>G	p.Arg405Gly	missense	Exon 3 of 20	ENSP00000490806.1	Q96PX9
	PLEKHG4B	ENST00000283426.11	TSL:1	c.145C>G	p.Arg49Gly	missense	Exon 1 of 18	ENSP00000283426.6	A0AAK2PKJ8
	PLEKHG4B	ENST00000924300.1		c.1213C>G	p.Arg405Gly	missense	Exon 3 of 20	ENSP00000594359.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.0060
DANN	Benign	0.46
DEOGEN2	Benign	0.011	T
Eigen	Benign	-2.2
Eigen_PC	Benign	-2.3
FATHMM_MKL	Benign	0.00079	N
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.00075	T
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		-3.5
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.038
Sift	Benign	0.28	T
Sift4G	Benign	0.25	T
Polyphen		0.0020	B
Vest4		0.050
MutPred		0.14		Loss of catalytic residue at R49 (P = 0.0361)
MVP		0.040
MPC		0.10
ClinPred		0.073	T
GERP RS		-4.9
PromoterAI		-0.0059	Neutral
Varity_R		0.033
gMVP		0.20
Mutation Taster		=100/0	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: rs1033372982; hg19: chr5-140567;