Variant 1-204223531-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_014935.5(PLEKHA6):c.3086C>T(p.Ala1029Val) variant causes a missense change. The variant allele was found at a frequency of 0.0084 in 1,550,594 control chromosomes in the GnomAD database, including 98 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0059 ( 9 hom., cov: 31)

Exomes 𝑓: 0.0087 ( 89 hom. )

Consequence

PLEKHA6
NM_014935.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.33

Variant links:

Genes affected

PLEKHA6 (HGNC:17053): (pleckstrin homology domain containing A6)

PLEKHA6 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=0.0027147233).

BP6

Variant 1-204223531-G-A is Benign according to our data. Variant chr1-204223531-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2639826.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLEKHA6	NM_014935.5 linkuse as main transcript	c.3086C>T	p.Ala1029Val	missense_variant	22/23	ENST00000272203.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
PLEKHA6	ENST00000272203.8 linkuse as main transcript	c.3086C>T	p.Ala1029Val	missense_variant	22/23	1	NM_014935.5	P2
PLEKHA6	ENST00000637508.1 linkuse as main transcript	c.3458C>T	p.Ala1153Val	missense_variant	26/27	5		A2
PLEKHA6	ENST00000414478.1 linkuse as main transcript	c.3146C>T	p.Ala1049Val	missense_variant	22/23	5

Frequencies

GnomAD3 genomes

AF:

0.00592

AC:

899

AN:

151802

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00131

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00558

Gnomad ASJ

AF:

0.0441

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00313

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00831

Gnomad OTH

AF:

0.00768

GnomAD3 exomes

AF:

0.00690

AC:

1084

AN:

157134

Hom.:

AF XY:

0.00715

AC XY:

591

AN XY:

82680

show subpopulations

Gnomad AFR exome

AF:

0.00149

Gnomad AMR exome

AF:

0.00255

Gnomad ASJ exome

AF:

0.0449

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00285

Gnomad FIN exome

AF:

0.00126

Gnomad NFE exome

AF:

0.00841

Gnomad OTH exome

AF:

0.00700

GnomAD4 exome

AF:

0.00867

AC:

12123

AN:

1398674

Hom.:

Cov.:

AF XY:

0.00847

AC XY:

5843

AN XY:

689916

show subpopulations

Gnomad4 AFR exome

AF:

0.00104

Gnomad4 AMR exome

AF:

0.00313

Gnomad4 ASJ exome

AF:

0.0471

Gnomad4 EAS exome

AF:

0.0000559

Gnomad4 SAS exome

AF:

0.00297

Gnomad4 FIN exome

AF:

0.00134

Gnomad4 NFE exome

AF:

0.00919

Gnomad4 OTH exome

AF:

0.00967

GnomAD4 genome

AF:

0.00592

AC:

899

AN:

151920

Hom.:

Cov.:

AF XY:

0.00536

AC XY:

398

AN XY:

74210

show subpopulations

Gnomad4 AFR

AF:

0.00130

Gnomad4 AMR

AF:

0.00557

Gnomad4 ASJ

AF:

0.0441

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00292

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.00833

Gnomad4 OTH

AF:

0.00760

Alfa

AF:

0.00939

Hom.:

Bravo

AF:

0.00644

TwinsUK

AF:

0.00944

AC:

ALSPAC

AF:

0.0104

AC:

ESP6500AA

AF:

0.00289

AC:

ESP6500EA

AF:

0.00870

AC:

ExAC

AF:

0.00329

AC:

277

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

PLEKHA6: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.68

Cadd

Benign

Dann

Benign

0.91

DEOGEN2

Benign

0.020

T;T;.

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.26

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.79

T;T;T

MetaRNN

Benign

0.0027

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.34

N;.;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.51

PROVEAN

Benign

0.030

N;.;N

REVEL

Benign

0.050

Sift

Benign

0.68

T;.;T

Sift4G

Benign

0.79

T;.;T

Polyphen

0.0

B;.;.

Vest4

0.091

MVP

0.043

MPC

0.10

ClinPred

0.0037

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.030

gMVP

0.20

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