Variant 16-67280887-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000379344.8(PLEKHG4):c.601C>T(p.Arg201Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00311 in 1,612,916 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0022 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0032 ( 17 hom. )

Consequence

PLEKHG4
ENST00000379344.8 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.86

Variant links:

Genes affected

PLEKHG4 (HGNC:24501): (pleckstrin homology and RhoGEF domain containing G4) The protein encoded by this gene can function as a guanine nucleotide exchange factor (GEF) and may play a role in intracellular signaling and cytoskeleton dynamics at the Golgi apparatus. Polymorphisms in the region of this gene have been found to be associated with spinocerebellar ataxia in some study populations. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

PLEKHG4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011156321).

BP6

Variant 16-67280887-C-T is Benign according to our data. Variant chr16-67280887-C-T is described in ClinVar as [Benign]. Clinvar id is 3341515.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLEKHG4	NM_001129729.3 linkuse as main transcript	c.601C>T	p.Arg201Trp	missense_variant	4/22	ENST00000379344.8	NP_001123201.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLEKHG4	ENST00000379344.8 linkuse as main transcript	c.601C>T	p.Arg201Trp	missense_variant	4/22	1	NM_001129729.3	ENSP00000368649	P2	Q58EX7-1

Frequencies

GnomAD3 genomes

AF:

0.00219

AC:

333

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000651

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.00720

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00387

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00185

AC:

462

AN:

250156

Hom.:

AF XY:

0.00208

AC XY:

281

AN XY:

135370

show subpopulations

Gnomad AFR exome

AF:

0.000370

Gnomad AMR exome

AF:

0.000520

Gnomad ASJ exome

AF:

0.00834

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00303

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.00321

AC:

4682

AN:

1460606

Hom.:

Cov.:

AF XY:

0.00311

AC XY:

2263

AN XY:

726680

show subpopulations

Gnomad4 AFR exome

AF:

0.000358

Gnomad4 AMR exome

AF:

0.000671

Gnomad4 ASJ exome

AF:

0.00826

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.0000575

Gnomad4 NFE exome

AF:

0.00379

Gnomad4 OTH exome

AF:

0.00325

GnomAD4 genome

AF:

0.00219

AC:

333

AN:

152310

Hom.:

Cov.:

AF XY:

0.00195

AC XY:

145

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.000649

Gnomad4 AMR

AF:

0.000784

Gnomad4 ASJ

AF:

0.00720

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00387

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00327

Hom.:

Bravo

AF:

0.00248

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00363

AC:

ESP6500AA

AF:

0.000910

AC:

ESP6500EA

AF:

0.00395

AC:

ExAC

AF:

0.00170

AC:

207

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00469

EpiControl

AF:

0.00362

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2024

PLEKHG4: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.076

BayesDel_noAF

Uncertain

0.12

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.52

D;T;D;D;.

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.41

.;T;.;D;D

M_CAP

Benign

0.054

MetaRNN

Benign

0.011

T;T;T;T;T

MetaSVM

Benign

-0.82

MutationAssessor

Pathogenic

3.4

M;.;M;M;.

MutationTaster

Benign

0.83

D;D;D;N

PrimateAI

Uncertain

0.59

PROVEAN

Pathogenic

-6.3

D;N;D;D;D

REVEL

Uncertain

0.35

Sift

Uncertain

0.0010

D;D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D;D

Polyphen

1.0

D;.;D;D;D

Vest4

0.85

MVP

0.72

MPC

0.95

ClinPred

0.11

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.29

gMVP

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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