Genetic Variant NM_052909.5:c.1145C>G (chr5-140384-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_052909.5(PLEKHG4B):c.1145C>G(p.Thr382Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000286 in 1,400,114 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

PLEKHG4B
NM_052909.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.27

Publications

0 publications found

Variant links:

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]

PLEKHG4B links:

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ACMG classification

Classification was made for transcript

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=0.046846867).

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.1145C>G	p.Thr382Ser	missense	Exon 3 of 20	NP_443141.4	Q96PX9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PLEKHG4B	ENST00000637938.2	TSL:5 MANE Select	c.1145C>G	p.Thr382Ser	missense	Exon 3 of 20	ENSP00000490806.1	Q96PX9
PLEKHG4B	ENST00000283426.11	TSL:1	c.77C>G	p.Thr26Ser	missense	Exon 1 of 18	ENSP00000283426.6	A0AAK2PKJ8
PLEKHG4B	ENST00000924300.1		c.1145C>G	p.Thr382Ser	missense	Exon 3 of 20	ENSP00000594359.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000641

AC:

AN:

155914

AF XY:

0.0000120

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000234

GnomAD4 exome

AF:

0.00000286

AC:

AN:

1400114

Hom.:

Cov.:

AF XY:

0.00000289

AC XY:

AN XY:

691114

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31860

American (AMR)

AF:

0.00

AC:

AN:

35844

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24642

East Asian (EAS)

AF:

0.00

AC:

AN:

36370

South Asian (SAS)

AF:

0.00

AC:

AN:

78968

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48250

Middle Eastern (MID)

AF:

0.000358

AC:

AN:

5586

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1080710

Other (OTH)

AF:

0.0000346

AC:

AN:

57884

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.31

(source)

DANN

Benign

0.66

DEOGEN2

Benign

0.0047

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.25

M_CAP

Benign

0.0011

MetaRNN

Benign

0.047

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.0

PhyloP100

-1.3

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.56

REVEL

Benign

0.047

Sift

Benign

0.86

Sift4G

Benign

0.64

Polyphen

0.0

Vest4

0.026

MutPred

0.12

Gain of glycosylation at T26 (P = 0.052)

MVP

0.14

MPC

0.073

ClinPred

0.026

GERP RS

-0.94

PromoterAI

-0.0038

Neutral

(source)

Varity_R

0.043

gMVP

0.098

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over