Variant 6-150733932-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001029884.3(PLEKHG1):c.251A>G(p.Glu84Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 0.000020 ( 0 hom. )

Consequence

PLEKHG1
NM_001029884.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.50

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:

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ACMG classification

Classification made for transcript

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=0.06780249).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLEKHG1	NM_001029884.3 linkuse as main transcript	c.251A>G	p.Glu84Gly	missense_variant	3/17	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.251A>G	p.Glu84Gly	missense_variant	3/17		NM_001029884.3	ENSP00000512689	P1
PLEKHG1	ENST00000358517.6 linkuse as main transcript	c.251A>G	p.Glu84Gly	missense_variant	2/16	5		ENSP00000351318	P1
PLEKHG1	ENST00000644968.1 linkuse as main transcript	c.251A>G	p.Glu84Gly	missense_variant	2/16			ENSP00000496254	P1
PLEKHG1	ENST00000644913.1 linkuse as main transcript	c.467A>G	p.Glu156Gly	missense_variant	2/2			ENSP00000493494

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000557

AC:

AN:

251308

Hom.:

AF XY:

0.0000589

AC XY:

AN XY:

135872

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000114

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000198

AC:

AN:

1461892

Hom.:

Cov.:

AF XY:

0.0000206

AC XY:

AN XY:

727246

show subpopulations

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:

0.0000252

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000741

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000237

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 31, 2022

The c.251A>G (p.E84G) alteration is located in exon 3 (coding exon 1) of the PLEKHG1 gene. This alteration results from a A to G substitution at nucleotide position 251, causing the glutamic acid (E) at amino acid position 84 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.45

CADD

Benign

7.5

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0071

T;.;T

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.61

.;T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.068

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

L;.;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.2

.;.;N

REVEL

Benign

0.043

Sift

Benign

0.24

.;.;T

Sift4G

Benign

0.23

.;.;T

Polyphen

0.0

B;.;B

Vest4

0.22

MutPred

0.25

Gain of glycosylation at S83 (P = 0.0345);.;Gain of glycosylation at S83 (P = 0.0345);

MVP

0.77

ClinPred

0.051

GERP RS

3.0

Varity_R

0.050

gMVP

0.24

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over