chr1-204223477-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014935.5(PLEKHA6):​c.3140G>A​(p.Arg1047Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000273 in 1,538,786 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

PLEKHA6
NM_014935.5 missense

Scores

2
5
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.82
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 Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.15886742).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PLEKHA6NM_014935.5 linkuse as main transcriptc.3140G>A p.Arg1047Gln 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.3140G>A p.Arg1047Gln missense_variant 22/231 NM_014935.5 ENSP00000272203 P2
PLEKHA6ENST00000637508.1 linkuse as main transcriptc.3512G>A p.Arg1171Gln missense_variant 26/275 ENSP00000490182 A2
PLEKHA6ENST00000414478.1 linkuse as main transcriptc.3200G>A p.Arg1067Gln missense_variant 22/235 ENSP00000402046

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
151964
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000484
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000190
AC:
3
AN:
158012
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
83078
show subpopulations
Gnomad AFR exome
AF:
0.000114
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000327
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000274
AC:
38
AN:
1386822
Hom.:
0
Cov.:
29
AF XY:
0.0000219
AC XY:
15
AN XY:
684826
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000347
Gnomad4 OTH exome
AF:
0.0000174
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
151964
Hom.:
0
Cov.:
31
AF XY:
0.0000269
AC XY:
2
AN XY:
74216
show subpopulations
Gnomad4 AFR
AF:
0.0000484
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000386
Hom.:
0
Bravo
AF:
0.0000189
ESP6500AA
AF:
0.000495
AC:
2
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000137
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJun 19, 2024The c.3140G>A (p.R1047Q) alteration is located in exon 22 (coding exon 20) of the PLEKHA6 gene. This alteration results from a G to A substitution at nucleotide position 3140, causing the arginine (R) at amino acid position 1047 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.16
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.42
CADD
Uncertain
25
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.023
T;T;.
Eigen
Uncertain
0.44
Eigen_PC
Uncertain
0.45
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Benign
0.46
T;T;T
M_CAP
Benign
0.024
T
MetaRNN
Benign
0.16
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.1
L;.;.
MutationTaster
Benign
0.68
D;D
PrimateAI
Uncertain
0.58
T
PROVEAN
Benign
-0.47
N;.;N
REVEL
Benign
0.088
Sift
Pathogenic
0.0
D;.;D
Sift4G
Uncertain
0.040
D;.;D
Polyphen
1.0
D;.;.
Vest4
0.23
MVP
0.093
MPC
0.57
ClinPred
0.92
D
GERP RS
4.6
Varity_R
0.29
gMVP
0.27

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.11
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: rs372291432; hg19: chr1-204192605; COSMIC: COSV55340747; API