chr1-204230511-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_014935.5(PLEKHA6):c.2485C>T(p.Arg829Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000308 in 1,591,104 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 0.000039 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000030 ( 0 hom. )
Consequence
PLEKHA6
NM_014935.5 missense
NM_014935.5 missense
Scores
4
7
8
Clinical Significance
Conservation
PhyloP100: 4.15
Genes affected
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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=0.2078656).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLEKHA6 | NM_014935.5 | c.2485C>T | p.Arg829Trp | missense_variant | 18/23 | ENST00000272203.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLEKHA6 | ENST00000272203.8 | c.2485C>T | p.Arg829Trp | missense_variant | 18/23 | 1 | NM_014935.5 | P2 | |
PLEKHA6 | ENST00000637508.1 | c.2857C>T | p.Arg953Trp | missense_variant | 22/27 | 5 | A2 | ||
PLEKHA6 | ENST00000414478.1 | c.2545C>T | p.Arg849Trp | missense_variant | 18/23 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152236Hom.: 0 Cov.: 33
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.0000470 AC: 10AN: 212678Hom.: 0 AF XY: 0.0000439 AC XY: 5AN XY: 113796
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GnomAD4 exome AF: 0.0000299 AC: 43AN: 1438868Hom.: 0 Cov.: 32 AF XY: 0.0000280 AC XY: 20AN XY: 713066
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GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152236Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74374
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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 | Sep 06, 2022 | The c.2485C>T (p.R829W) alteration is located in exon 18 (coding exon 16) of the PLEKHA6 gene. This alteration results from a C to T substitution at nucleotide position 2485, causing the arginine (R) at amino acid position 829 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Benign
T;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;.;D
REVEL
Benign
Sift
Pathogenic
D;.;D
Sift4G
Uncertain
D;.;D
Polyphen
D;.;.
Vest4
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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