rs1033372982

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr5-140452-C-G
• chr5-140452-C-T

Variant summary

Our verdict is Likely benign. Variant got -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. 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.

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

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

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=0.04678297).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLEKHG4B	NM_052909.5	c.1213C>G	p.Arg405Gly	missense_variant	Exon 3 of 20	ENST00000637938.2	NP_443141.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLEKHG4B	ENST00000637938.2	c.1213C>G	p.Arg405Gly	missense_variant	Exon 3 of 20	5	NM_052909.5	ENSP00000490806.1
PLEKHG4B	ENST00000283426.11	c.145C>G	p.Arg49Gly	missense_variant	Exon 1 of 18	1		ENSP00000283426.6
PLEKHG4B	ENST00000502646.1	c.-114C>G		upstream_gene_variant		1		ENSP00000422493.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T
M_CAP	Benign	0.00075	T
MetaRNN	Benign	0.047	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	.;N
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
Varity_R		0.033
gMVP		0.20

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

LitVar

Other links and lift over

dbSNP: rs1033372982; hg19: chr5-140567;