Variant 12-19274579-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001256470.2(PLEKHA5):c.909A>G(p.Arg303=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0117 in 1,613,522 control chromosomes in the GnomAD database, including 126 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0081 ( 6 hom., cov: 32)

Exomes 𝑓: 0.012 ( 120 hom. )

Consequence

PLEKHA5
NM_001256470.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.68

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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 12-19274579-A-G is Benign according to our data. Variant chr12-19274579-A-G is described in ClinVar as [Benign]. Clinvar id is 781698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.68 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLEKHA5	NM_001256470.2 linkuse as main transcript	c.909A>G	p.Arg303=	synonymous_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.909A>G	p.Arg303=	synonymous_variant	11/32	1	NM_001256470.2	A2	Q9HAU0-6

Frequencies

GnomAD3 genomes

AF:

0.00813

AC:

1237

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00256

Gnomad AMI

AF:

0.0175

Gnomad AMR

AF:

0.00988

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00436

Gnomad FIN

AF:

0.00151

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0134

Gnomad OTH

AF:

0.00718

GnomAD3 exomes

AF:

0.00736

AC:

1846

AN:

250786

Hom.:

AF XY:

0.00789

AC XY:

1070

AN XY:

135598

show subpopulations

Gnomad AFR exome

AF:

0.00166

Gnomad AMR exome

AF:

0.00548

Gnomad ASJ exome

AF:

0.000993

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00634

Gnomad FIN exome

AF:

0.00204

Gnomad NFE exome

AF:

0.0118

Gnomad OTH exome

AF:

0.00769

GnomAD4 exome

AF:

0.0121

AC:

17661

AN:

1461200

Hom.:

120

Cov.:

AF XY:

0.0120

AC XY:

8700

AN XY:

726968

show subpopulations

Gnomad4 AFR exome

AF:

0.00204

Gnomad4 AMR exome

AF:

0.00535

Gnomad4 ASJ exome

AF:

0.00107

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00714

Gnomad4 FIN exome

AF:

0.00210

Gnomad4 NFE exome

AF:

0.0143

Gnomad4 OTH exome

AF:

0.0104

GnomAD4 genome

AF:

0.00812

AC:

1237

AN:

152322

Hom.:

Cov.:

AF XY:

0.00773

AC XY:

576

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00255

Gnomad4 AMR

AF:

0.00987

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00457

Gnomad4 FIN

AF:

0.00151

Gnomad4 NFE

AF:

0.0134

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.0101

Hom.:

Bravo

AF:

0.00806

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.0129

EpiControl

AF:

0.0117

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 29, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

PLEKHA5-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 29, 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

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.64

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