Variant 14-64730816-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001308147.2(PLEKHG3):c.584C>T(p.Thr195Met) variant causes a missense change. The variant allele was found at a frequency of 0.00117 in 1,613,452 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0018 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 17 hom. )

Consequence

PLEKHG3
NM_001308147.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 6.09

Variant links:

Genes affected

PLEKHG3 (HGNC:20364): (pleckstrin homology and RhoGEF domain containing G3) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of small GTPase mediated signal transduction. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

PLEKHG3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010800958).

BP6

Variant 14-64730816-C-T is Benign according to our data. Variant chr14-64730816-C-T is described in ClinVar as [Benign]. Clinvar id is 789061.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.00111 (1622/1461156) while in subpopulation EAS AF= 0.0195 (775/39690). AF 95% confidence interval is 0.0184. There are 17 homozygotes in gnomad4_exome. There are 749 alleles in male gnomad4_exome subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLEKHG3	NM_001308147.2 link	c.584C>T	p.Thr195Met	missense_variant	6/17	ENST00000247226.13	NP_001295076.1	A1L390-1A0A2X0SFH4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLEKHG3	ENST00000247226.13 link	c.584C>T	p.Thr195Met	missense_variant	6/17	1	NM_001308147.2	ENSP00000247226.8		A1L390-1

Frequencies

GnomAD3 genomes

AF:

0.00179

AC:

273

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0104

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.0154

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00380

AC:

952

AN:

250598

Hom.:

AF XY:

0.00320

AC XY:

434

AN XY:

135496

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.0153

Gnomad ASJ exome

AF:

0.00288

Gnomad EAS exome

AF:

0.0189

Gnomad SAS exome

AF:

0.000490

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000106

Gnomad OTH exome

AF:

0.00229

GnomAD4 exome

AF:

0.00111

AC:

1622

AN:

1461156

Hom.:

Cov.:

AF XY:

0.00103

AC XY:

749

AN XY:

726866

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.0135

Gnomad4 ASJ exome

AF:

0.00222

Gnomad4 EAS exome

AF:

0.0195

Gnomad4 SAS exome

AF:

0.000545

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000747

Gnomad4 OTH exome

AF:

0.000795

GnomAD4 genome

AF:

0.00179

AC:

272

AN:

152296

Hom.:

Cov.:

AF XY:

0.00242

AC XY:

180

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.000361

Gnomad4 AMR

AF:

0.0103

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.0157

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00121

Hom.:

Bravo

AF:

0.00296

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.00334

AC:

405

Asia WGS

AF:

0.00606

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Sep 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.10

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.086

T;.;T

Eigen

Pathogenic

0.72

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.98

D;D;D

MetaRNN

Benign

0.011

T;T;T

MetaSVM

Uncertain

-0.22

MutationAssessor

Uncertain

2.3

.;.;M

PrimateAI

Uncertain

0.62

REVEL

Uncertain

0.38

Sift4G

Uncertain

0.0080

D;D;D

Polyphen

1.0

.;D;D

Vest4

0.67, 0.65

MVP

0.86

MPC

0.63

ClinPred

0.037

GERP RS

4.9

Varity_R

0.73

gMVP

0.29

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over