5-140527-G-T

Variant names:

• chr5-140527-G-T
• NM_052909.5:c.1288G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_052909.5(PLEKHG4B):​c.1288G>T​(p.Gly430Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,447,284 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PLEKHG4B NM_052909.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.417

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16682747).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLEKHG4B	NM_052909.5	c.1288G>T	p.Gly430Trp	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.1288G>T	p.Gly430Trp	missense_variant	Exon 3 of 20	5	NM_052909.5	ENSP00000490806.1
PLEKHG4B	ENST00000283426.11	c.220G>T	p.Gly74Trp	missense_variant	Exon 1 of 18	1		ENSP00000283426.6
PLEKHG4B	ENST00000502646.1	c.-39G>T		upstream_gene_variant		1		ENSP00000422493.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1447284 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 718678

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.04e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.010	.;T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.57	T;T
M_CAP	Benign	0.0093	T
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	.;N
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-2.4	.;N
REVEL	Benign	0.051
Sift	Uncertain	0.0030	.;D
Sift4G	Uncertain	0.026	.;D
Polyphen		0.96	.;D
Vest4		0.21
MutPred		0.22		.;Loss of methylation at R75 (P = 0.0217);
MVP		0.27
MPC		0.42
ClinPred		0.45	T
GERP RS		-0.21
Varity_R		0.10
gMVP		0.31

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: chr5-140642;