Variant 5-143200-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_052909.5(PLEKHG4B):c.1631A>G(p.Lys544Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000123 in 1,459,274 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 Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

PLEKHG4B
NM_052909.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.00700

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 made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.017179638).

BP6

Variant 5-143200-A-G is Benign according to our data. Variant chr5-143200-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3214997.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLEKHG4B	NM_052909.5 linkuse as main transcript	c.1631A>G	p.Lys544Arg	missense_variant	4/20	ENST00000637938.2	NP_443141.4	Q96PX9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PLEKHG4B	ENST00000637938.2 linkuse as main transcript	c.1631A>G	p.Lys544Arg	missense_variant	4/20	5	NM_052909.5	ENSP00000490806.1	A0A1B0GW72
PLEKHG4B	ENST00000283426.11 linkuse as main transcript	c.563A>G	p.Lys188Arg	missense_variant	2/18	1		ENSP00000283426.6	Q96PX9
PLEKHG4B	ENST00000502646.1 linkuse as main transcript	c.305A>G	p.Lys102Arg	missense_variant	2/9	1		ENSP00000422493.1	Q96HN1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000524

AC:

AN:

248324

Hom.:

AF XY:

0.0000445

AC XY:

AN XY:

134956

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000710

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000123

AC:

AN:

1459274

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

726002

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000403

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000340

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 21, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.35

DANN

Benign

0.38

DEOGEN2

Benign

0.0042

.;T;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.034

LIST_S2

Benign

0.34

T;T;T

M_CAP

Benign

0.0014

MetaRNN

Benign

0.017

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.0

.;N;.

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.18

.;N;N

REVEL

Benign

0.011

Sift

Benign

0.53

.;T;T

Sift4G

Benign

0.64

.;T;T

Polyphen

0.0

.;B;.

Vest4

0.014

MutPred

0.18

.;Loss of ubiquitination at K188 (P = 0.0071);.;

MVP

0.12

MPC

0.067

ClinPred

0.0067

GERP RS

-2.9

Varity_R

0.032

gMVP

0.15

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