10-122406615-A-G
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001001974.4(PLEKHA1):āc.284A>Gā(p.Asn95Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000632 in 1,613,422 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 (ā ).
Frequency
Genomes: š 0.000079 ( 0 hom., cov: 32)
Exomes š: 0.000062 ( 0 hom. )
Consequence
PLEKHA1
NM_001001974.4 missense
NM_001001974.4 missense
Scores
1
9
9
Clinical Significance
Conservation
PhyloP100: 8.82
Genes affected
PLEKHA1 (HGNC:14335): (pleckstrin homology domain containing A1) This gene encodes a pleckstrin homology domain-containing adapter protein. The encoded protein is localized to the plasma membrane where it specifically binds phosphatidylinositol 3,4-bisphosphate. This protein may be involved in the formation of signaling complexes in the plasma membrane. Polymorphisms in this gene are associated with age-related macular degeneration. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 5.[provided by RefSeq, Sep 2010]
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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=0.2961105).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PLEKHA1 | NM_001001974.4 | c.284A>G | p.Asn95Ser | missense_variant | 5/12 | ENST00000368990.8 | NP_001001974.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PLEKHA1 | ENST00000368990.8 | c.284A>G | p.Asn95Ser | missense_variant | 5/12 | 1 | NM_001001974.4 | ENSP00000357986 | P3 |
Frequencies
GnomAD3 genomes AF: 0.0000788 AC: 12AN: 152228Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000716 AC: 18AN: 251286Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135820
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GnomAD4 exome AF: 0.0000616 AC: 90AN: 1461076Hom.: 0 Cov.: 30 AF XY: 0.0000660 AC XY: 48AN XY: 726902
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GnomAD4 genome AF: 0.0000788 AC: 12AN: 152346Hom.: 0 Cov.: 32 AF XY: 0.0000671 AC XY: 5AN XY: 74494
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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 | Feb 16, 2023 | The c.284A>G (p.N95S) alteration is located in exon 5 (coding exon 4) of the PLEKHA1 gene. This alteration results from a A to G substitution at nucleotide position 284, causing the asparagine (N) at amino acid position 95 to be replaced by a serine (S). 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
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
D;T;.;D;.;D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
.;D;D;.;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;.;M;M;M
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;.;D;D;D
REVEL
Uncertain
Sift
Benign
T;T;.;T;T;T
Sift4G
Benign
T;T;T;T;T;T
Polyphen
B;.;.;B;.;B
Vest4
MVP
MPC
ClinPred
T
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