chr10-122429909-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001001974.4(PLEKHA1):c.1186G>A(p.Asp396Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000684 in 1,461,552 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: not found (cov: 32)
Exomes 𝑓: 0.0000068 ( 0 hom. )
Consequence
PLEKHA1
NM_001001974.4 missense
NM_001001974.4 missense
Scores
4
14
Clinical Significance
Conservation
PhyloP100: 6.47
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 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.19984725).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLEKHA1 | NM_001001974.4 | c.1186G>A | p.Asp396Asn | missense_variant | 12/12 | ENST00000368990.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLEKHA1 | ENST00000368990.8 | c.1186G>A | p.Asp396Asn | missense_variant | 12/12 | 1 | NM_001001974.4 | P3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250790Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135522
GnomAD3 exomes
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GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461552Hom.: 0 Cov.: 33 AF XY: 0.00000550 AC XY: 4AN XY: 727072
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727072
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
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Cov.:
32
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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 submitter | clinical testing | Ambry Genetics | Oct 25, 2022 | The c.1186G>A (p.D396N) alteration is located in exon 12 (coding exon 11) of the PLEKHA1 gene. This alteration results from a G to A substitution at nucleotide position 1186, causing the aspartic acid (D) at amino acid position 396 to be replaced by an asparagine (N). 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
Benign
T;T;T
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;L
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.;N
REVEL
Benign
Sift
Benign
T;.;T
Sift4G
Benign
T;T;T
Polyphen
P;P;P
Vest4
MutPred
Loss of phosphorylation at S398 (P = 0.0746);Loss of phosphorylation at S398 (P = 0.0746);Loss of phosphorylation at S398 (P = 0.0746);
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