Variant rs61742396 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001029884.3(PLEKHG1):c.3242G>A(p.Gly1081Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0408 in 1,613,938 control chromosomes in the GnomAD database, including 1,507 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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: 𝑓 0.033 ( 95 hom., cov: 33)

Exomes 𝑓: 0.042 ( 1412 hom. )

Consequence

PLEKHG1
NM_001029884.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.21

Variant links:

Genes affected

PLEKHG1 (HGNC:20884): (pleckstrin homology and RhoGEF domain containing G1) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of small GTPase mediated signal transduction. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

PLEKHG1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016655028).

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLEKHG1	NM_001029884.3 linkuse as main transcript	c.3242G>A	p.Gly1081Glu	missense_variant	17/17	ENST00000696526.1	NP_001025055.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
PLEKHG1	ENST00000696526.1 linkuse as main transcript	c.3242G>A	p.Gly1081Glu	missense_variant	17/17		NM_001029884.3	ENSP00000512689	P1
PLEKHG1	ENST00000475490.1 linkuse as main transcript	c.1158-1055G>A		intron_variant, NMD_transcript_variant		1		ENSP00000433107
PLEKHG1	ENST00000358517.6 linkuse as main transcript	c.3242G>A	p.Gly1081Glu	missense_variant	16/16	5		ENSP00000351318	P1
PLEKHG1	ENST00000644968.1 linkuse as main transcript	c.3242G>A	p.Gly1081Glu	missense_variant	16/16			ENSP00000496254	P1

Frequencies

GnomAD3 genomes

AF:

0.0329

AC:

5004

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0205

Gnomad AMI

AF:

0.0175

Gnomad AMR

AF:

0.0281

Gnomad ASJ

AF:

0.0712

Gnomad EAS

AF:

0.0197

Gnomad SAS

AF:

0.0549

Gnomad FIN

AF:

0.0151

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0418

Gnomad OTH

AF:

0.0373

GnomAD3 exomes

AF:

0.0358

AC:

8991

AN:

251328

Hom.:

210

AF XY:

0.0375

AC XY:

5099

AN XY:

135832

show subpopulations

Gnomad AFR exome

AF:

0.0218

Gnomad AMR exome

AF:

0.0245

Gnomad ASJ exome

AF:

0.0592

Gnomad EAS exome

AF:

0.0204

Gnomad SAS exome

AF:

0.0520

Gnomad FIN exome

AF:

0.0184

Gnomad NFE exome

AF:

0.0401

Gnomad OTH exome

AF:

0.0447

GnomAD4 exome

AF:

0.0416

AC:

60793

AN:

1461690

Hom.:

1412

Cov.:

AF XY:

0.0421

AC XY:

30620

AN XY:

727162

show subpopulations

Gnomad4 AFR exome

AF:

0.0215

Gnomad4 AMR exome

AF:

0.0248

Gnomad4 ASJ exome

AF:

0.0633

Gnomad4 EAS exome

AF:

0.0253

Gnomad4 SAS exome

AF:

0.0510

Gnomad4 FIN exome

AF:

0.0171

Gnomad4 NFE exome

AF:

0.0432

Gnomad4 OTH exome

AF:

0.0428

GnomAD4 genome

AF:

0.0330

AC:

5017

AN:

152248

Hom.:

Cov.:

AF XY:

0.0314

AC XY:

2339

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0205

Gnomad4 AMR

AF:

0.0280

Gnomad4 ASJ

AF:

0.0712

Gnomad4 EAS

AF:

0.0197

Gnomad4 SAS

AF:

0.0551

Gnomad4 FIN

AF:

0.0151

Gnomad4 NFE

AF:

0.0417

Gnomad4 OTH

AF:

0.0436

Alfa

AF:

0.0421

Hom.:

246

Bravo

AF:

0.0325

TwinsUK

AF:

0.0472

AC:

175

ALSPAC

AF:

0.0413

AC:

159

ESP6500AA

AF:

0.0236

AC:

104

ESP6500EA

AF:

0.0397

AC:

341

ExAC

AF:

0.0360

AC:

4366

Asia WGS

AF:

0.0590

AC:

205

AN:

3478

EpiCase

AF:

0.0431

EpiControl

AF:

0.0439

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.20

DEOGEN2

Benign

0.0014

T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.099

LIST_S2

Benign

0.35

.;T

MetaRNN

Benign

0.0017

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-2.2

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.39

PROVEAN

Benign

1.8

.;N

REVEL

Benign

0.14

Sift

Benign

1.0

.;T

Sift4G

Benign

1.0

.;T

Polyphen

0.0

B;B

Vest4

0.074

ClinPred

0.0050

GERP RS

5.8

Varity_R

0.042

gMVP

0.10

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over