Variant 12-19274803-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001256470.2(PLEKHA5):c.1133G>A(p.Ser378Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00042 in 1,614,168 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00030 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00043 ( 12 hom. )

Consequence

PLEKHA5
NM_001256470.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.738

Variant links:

Genes affected

PLEKHA5 (HGNC:30036): (pleckstrin homology domain containing A5) Predicted to enable phosphatidylinositol phosphate binding activity. Predicted to act upstream of or within reproductive system development. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

PLEKHA5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003682524).

BP6

Variant 12-19274803-G-A is Benign according to our data. Variant chr12-19274803-G-A is described in ClinVar as [Benign]. Clinvar id is 3034315.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLEKHA5	NM_001256470.2 linkuse as main transcript	c.1133G>A	p.Ser378Asn	missense_variant	11/32	ENST00000429027.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLEKHA5	ENST00000429027.7 linkuse as main transcript	c.1133G>A	p.Ser378Asn	missense_variant	11/32	1	NM_001256470.2	A2	Q9HAU0-6

Frequencies

GnomAD3 genomes

AF:

0.000302

AC:

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00952

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000899

AC:

226

AN:

251404

Hom.:

AF XY:

0.00134

AC XY:

182

AN XY:

135878

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:

0.00725

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000432

AC:

632

AN:

1461888

Hom.:

Cov.:

AF XY:

0.000677

AC XY:

492

AN XY:

727248

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:

0.00708

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000298

GnomAD4 genome

AF:

0.000302

AC:

AN:

152280

Hom.:

Cov.:

AF XY:

0.000457

AC XY:

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00953

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000125

Hom.:

Bravo

AF:

0.0000416

ExAC

AF:

0.00105

AC:

128

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

PLEKHA5-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 06, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.055

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.79

Cadd

Benign

0.34

Dann

Benign

0.23

Eigen

Benign

-1.2

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.73

T;T;T;T;T;T

MetaRNN

Benign

0.0037

T;T;T;T;T;T

MetaSVM

Benign

-0.95

MutationTaster

Benign

0.99

N;N;N;N;N;N;N;N;N;N

PrimateAI

Benign

0.37

PROVEAN

Benign

1.2

N;N;N;N;N;N

REVEL

Benign

0.043

Sift

Benign

1.0

T;T;T;T;T;T

Sift4G

Benign

0.59

T;T;T;T;T;T

Polyphen

0.0

.;.;B;B;.;.

Vest4

0.087

MVP

0.15

MPC

0.052

ClinPred

0.018

GERP RS

2.9

Varity_R

0.034

gMVP

0.061

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