chr12-19274803-G-A
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_001256470.2(PLEKHA5):c.1133G>A(p.Ser378Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00042 in 1,614,168 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).
Frequency
Genomes: 𝑓 0.00030 ( 2 hom., cov: 32)
Exomes 𝑓: 0.00043 ( 12 hom. )
Consequence
PLEKHA5
NM_001256470.2 missense
NM_001256470.2 missense
Scores
18
Clinical Significance
Conservation
PhyloP100: 0.738
Genes affected
PLEKHA5 (HGNC:30036): (pleckstrin homology domain containing A5) Predicted to enable phosphatidylinositol phosphate binding activity. Predicted to act upstream of or within reproductive system development. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.003682524).
BP6
Variant 12-19274803-G-A is Benign according to our data. Variant chr12-19274803-G-A is described in ClinVar as [Benign]. Clinvar id is 3034315.Status of the report is no_assertion_criteria_provided, 0 stars.
BS2
High Homozygotes in GnomAd4 at 2 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLEKHA5 | NM_001256470.2 | c.1133G>A | p.Ser378Asn | missense_variant | 11/32 | ENST00000429027.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLEKHA5 | ENST00000429027.7 | c.1133G>A | p.Ser378Asn | missense_variant | 11/32 | 1 | NM_001256470.2 | A2 |
Frequencies
GnomAD3 genomes AF: 0.000302 AC: 46AN: 152162Hom.: 2 Cov.: 32
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GnomAD3 exomes AF: 0.000899 AC: 226AN: 251404Hom.: 2 AF XY: 0.00134 AC XY: 182AN XY: 135878
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GnomAD4 exome AF: 0.000432 AC: 632AN: 1461888Hom.: 12 Cov.: 33 AF XY: 0.000677 AC XY: 492AN XY: 727248
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GnomAD4 genome AF: 0.000302 AC: 46AN: 152280Hom.: 2 Cov.: 32 AF XY: 0.000457 AC XY: 34AN XY: 74464
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
PLEKHA5-related disorder Benign:1
Benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 06, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
.;T;T;.;.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;T;T;T;T
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;.;N;N;.;.
MutationTaster
Benign
N;N;N;N;N;N;N;N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;T;T;T
Sift4G
Benign
T;T;T;T;T;T
Polyphen
0.0
.;.;B;B;.;.
Vest4
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MPC
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T
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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