chr1-204229100-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_014935.5(PLEKHA6):c.2588G>A(p.Arg863His) variant causes a missense change. The variant allele was found at a frequency of 0.0000583 in 1,612,072 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000062 ( 0 hom. )
Consequence
PLEKHA6
NM_014935.5 missense
NM_014935.5 missense
Scores
6
5
8
Clinical Significance
Conservation
PhyloP100: 6.36
Genes affected
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PLEKHA6 | NM_014935.5 | c.2588G>A | p.Arg863His | missense_variant | 19/23 | ENST00000272203.8 | NP_055750.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PLEKHA6 | ENST00000272203.8 | c.2588G>A | p.Arg863His | missense_variant | 19/23 | 1 | NM_014935.5 | ENSP00000272203 | P2 | |
PLEKHA6 | ENST00000637508.1 | c.2960G>A | p.Arg987His | missense_variant | 23/27 | 5 | ENSP00000490182 | A2 | ||
PLEKHA6 | ENST00000414478.1 | c.2648G>A | p.Arg883His | missense_variant | 19/23 | 5 | ENSP00000402046 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152130Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000241 AC: 6AN: 249286Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 134988
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GnomAD4 exome AF: 0.0000623 AC: 91AN: 1459824Hom.: 0 Cov.: 34 AF XY: 0.0000454 AC XY: 33AN XY: 726272
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152248Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74432
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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 submitter | clinical testing | Ambry Genetics | Dec 21, 2023 | The c.2588G>A (p.R863H) alteration is located in exon 19 (coding exon 17) of the PLEKHA6 gene. This alteration results from a G to A substitution at nucleotide position 2588, causing the arginine (R) at amino acid position 863 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;.
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;.;N
REVEL
Benign
Sift
Uncertain
D;.;D
Sift4G
Uncertain
D;.;D
Polyphen
D;.;.
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at