Variant 12-19274830-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001256470.2(PLEKHA5):c.1160T>C(p.Val387Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0105 in 1,614,174 control chromosomes in the GnomAD database, including 198 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 (no stars).

Frequency

Genomes: 𝑓 0.010 ( 27 hom., cov: 32)

Exomes 𝑓: 0.011 ( 171 hom. )

Consequence

PLEKHA5
NM_001256470.2 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.87

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0020955503).

BP6

Variant 12-19274830-T-C is Benign according to our data. Variant chr12-19274830-T-C is described in ClinVar as [Benign]. Clinvar id is 3057185.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00998 (1520/152306) while in subpopulation EAS AF= 0.0506 (262/5174). AF 95% confidence interval is 0.0456. There are 27 homozygotes in gnomad4. There are 818 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 27 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLEKHA5	NM_001256470.2 linkuse as main transcript	c.1160T>C	p.Val387Ala	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.1160T>C	p.Val387Ala	missense_variant	11/32	1	NM_001256470.2	A2	Q9HAU0-6

Frequencies

GnomAD3 genomes

AF:

0.00995

AC:

1515

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00198

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0223

Gnomad ASJ

AF:

0.0351

Gnomad EAS

AF:

0.0511

Gnomad SAS

AF:

0.0369

Gnomad FIN

AF:

0.00509

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00647

Gnomad OTH

AF:

0.0148

GnomAD3 exomes

AF:

0.0169

AC:

4255

AN:

251328

Hom.:

AF XY:

0.0180

AC XY:

2445

AN XY:

135844

show subpopulations

Gnomad AFR exome

AF:

0.00160

Gnomad AMR exome

AF:

0.0243

Gnomad ASJ exome

AF:

0.0326

Gnomad EAS exome

AF:

0.0542

Gnomad SAS exome

AF:

0.0334

Gnomad FIN exome

AF:

0.00337

Gnomad NFE exome

AF:

0.00754

Gnomad OTH exome

AF:

0.0183

GnomAD4 exome

AF:

0.0105

AC:

15377

AN:

1461868

Hom.:

171

Cov.:

AF XY:

0.0114

AC XY:

8310

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.00245

Gnomad4 AMR exome

AF:

0.0221

Gnomad4 ASJ exome

AF:

0.0315

Gnomad4 EAS exome

AF:

0.0394

Gnomad4 SAS exome

AF:

0.0330

Gnomad4 FIN exome

AF:

0.00341

Gnomad4 NFE exome

AF:

0.00704

Gnomad4 OTH exome

AF:

0.0150

GnomAD4 genome

AF:

0.00998

AC:

1520

AN:

152306

Hom.:

Cov.:

AF XY:

0.0110

AC XY:

818

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00200

Gnomad4 AMR

AF:

0.0222

Gnomad4 ASJ

AF:

0.0351

Gnomad4 EAS

AF:

0.0506

Gnomad4 SAS

AF:

0.0371

Gnomad4 FIN

AF:

0.00509

Gnomad4 NFE

AF:

0.00648

Gnomad4 OTH

AF:

0.0175

Alfa

AF:

0.0100

Hom.:

Bravo

AF:

0.0101

TwinsUK

AF:

0.00755

AC:

ALSPAC

AF:

0.00597

AC:

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.00884

AC:

ExAC

AF:

0.0160

AC:

1944

Asia WGS

AF:

0.0630

AC:

219

AN:

3478

EpiCase

AF:

0.00802

EpiControl

AF:

0.0103

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PLEKHA5-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 19, 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

0.15

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.82

DEOGEN2

Benign

0.0085

.;T;T;.;.;T

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.24

FATHMM_MKL

Benign

0.40

LIST_S2

Uncertain

0.89

D;D;D;D;D;D

MetaRNN

Benign

0.0021

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

.;.;L;L;.;.

MutationTaster

Benign

1.0

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

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.72

N;N;N;N;N;N

REVEL

Benign

0.062

Sift

Benign

0.57

T;T;T;T;T;T

Sift4G

Benign

0.44

T;T;T;T;T;T

Polyphen

0.047, 0.041

.;.;B;B;.;.

Vest4

0.18

MPC

0.11

ClinPred

0.031

GERP RS

5.3

Varity_R

0.11

gMVP

0.16

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