chr1-204223531-G-A

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

2
16

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)

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 GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PLEKHA6NM_014935.5 linkuse as main transcriptc.3086C>T p.Ala1029Val missense_variant 22/23 ENST00000272203.8 NP_055750.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PLEKHA6ENST00000272203.8 linkuse as main transcriptc.3086C>T p.Ala1029Val missense_variant 22/231 NM_014935.5 ENSP00000272203 P2
PLEKHA6ENST00000637508.1 linkuse as main transcriptc.3458C>T p.Ala1153Val missense_variant 26/275 ENSP00000490182 A2
PLEKHA6ENST00000414478.1 linkuse as main transcriptc.3146C>T p.Ala1049Val missense_variant 22/235 ENSP00000402046

Frequencies

GnomAD3 genomes
AF:
0.00592
AC:
899
AN:
151802
Hom.:
8
Cov.:
31
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.:
20
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.:
89
Cov.:
31
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.:
9
Cov.:
31
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.:
9
Bravo
AF:
0.00644
TwinsUK
AF:
0.00944
AC:
35
ALSPAC
AF:
0.0104
AC:
40
ESP6500AA
AF:
0.00289
AC:
12
ESP6500EA
AF:
0.00870
AC:
70
ExAC
AF:
0.00329
AC:
277
Asia WGS
AF:
0.00144
AC:
6
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 submitterclinical testingCeGaT Center for Human Genetics TuebingenDec 01, 2022PLEKHA6: BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.084
BayesDel_addAF
Benign
-0.64
T
BayesDel_noAF
Benign
-0.68
CADD
Benign
23
DANN
Benign
0.91
DEOGEN2
Benign
0.020
T;T;.
Eigen
Benign
-0.46
Eigen_PC
Benign
-0.26
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Benign
0.79
T;T;T
MetaRNN
Benign
0.0027
T;T;T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
0.34
N;.;.
MutationTaster
Benign
1.0
N;N
PrimateAI
Uncertain
0.51
T
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
T
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.

Other links and lift over

dbSNP: rs145148095; hg19: chr1-204192659; COSMIC: COSV55330788; API