1-204229091-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_014935.5(PLEKHA6):c.2597G>A(p.Arg866His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000304 in 1,612,816 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 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000033 ( 0 hom. )
Consequence
PLEKHA6
NM_014935.5 missense
NM_014935.5 missense
Scores
5
3
11
Clinical Significance
Conservation
PhyloP100: 3.52
Genes affected
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.35048223).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PLEKHA6 | NM_014935.5 | c.2597G>A | p.Arg866His | 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.2597G>A | p.Arg866His | missense_variant | 19/23 | 1 | NM_014935.5 | ENSP00000272203 | P2 | |
PLEKHA6 | ENST00000637508.1 | c.2969G>A | p.Arg990His | missense_variant | 23/27 | 5 | ENSP00000490182 | A2 | ||
PLEKHA6 | ENST00000414478.1 | c.2657G>A | p.Arg886His | missense_variant | 19/23 | 5 | ENSP00000402046 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152164Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000160 AC: 4AN: 250106Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135328
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GnomAD4 exome AF: 0.0000329 AC: 48AN: 1460652Hom.: 0 Cov.: 34 AF XY: 0.0000303 AC XY: 22AN XY: 726674
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152164Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74334
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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 | Mar 24, 2023 | The c.2597G>A (p.R866H) 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 2597, causing the arginine (R) at amino acid position 866 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
Benign
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
Pathogenic
D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.;N
REVEL
Benign
Sift
Benign
D;.;D
Sift4G
Uncertain
D;.;T
Polyphen
D;.;.
Vest4
MutPred
Loss of MoRF binding (P = 0.0272);.;.;
MVP
MPC
ClinPred
D
GERP RS
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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