PLEKHG4B p.Thr382Ser

Variant names:

• chr5-140383-A-T
• NM_052909.5:c.1144A>T
• PLEKHG4B p.Thr382Ser

Your query was ambiguous. Multiple possible variants found:

• chr5-140383-A-T
• chr5-140384-C-G
• chr5-140383-ACT-TCC
• chr5-140383-ACT-TCA
• chr5-140383-ACT-TCG
• chr5-140384-CT-GC

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.1144A>T​(p.Thr382Ser) 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PLEKHG4B NM_052909.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.176
• 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=0.034582466).

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.1144A>T	p.Thr382Ser	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.1144A>T	p.Thr382Ser	missense	Exon 3 of 20	ENSP00000490806.1	Q96PX9
	PLEKHG4B	ENST00000283426.11	TSL:1	c.76A>T	p.Thr26Ser	missense	Exon 1 of 18	ENSP00000283426.6	A0AAK2PKJ8
	PLEKHG4B	ENST00000924300.1		c.1144A>T	p.Thr382Ser	missense	Exon 3 of 20	ENSP00000594359.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.11
DANN	Benign	0.66
DEOGEN2	Benign	0.0047	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.058	N
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.18
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.56	N
REVEL	Benign	0.025
Sift	Benign	0.86	T
Sift4G	Benign	0.64	T
PromoterAI		-0.0018	Neutral
Varity_R		0.033
gMVP		0.098
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr5-140498;