14-22973562-G-A
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_032876.6(AJUBA):c.1498C>T(p.Arg500Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000222 in 1,614,072 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 0.00012 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00023 ( 0 hom. )
Consequence
AJUBA
NM_032876.6 missense
NM_032876.6 missense
Scores
3
11
4
Clinical Significance
Conservation
PhyloP100: 3.74
Genes affected
AJUBA (HGNC:20250): (ajuba LIM protein) Enables alpha-catenin binding activity and transcription corepressor activity. Involved in several processes, including negative regulation of hippo signaling; positive regulation of gene silencing by miRNA; and regulation of cellular response to hypoxia. Acts upstream of or within gene silencing by miRNA and positive regulation of protein-containing complex assembly. Located in several cellular components, including Golgi apparatus; P-body; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.37483233).
BS2
High AC in GnomAd4 at 18 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AJUBA | NM_032876.6 | c.1498C>T | p.Arg500Trp | missense_variant | 8/8 | ENST00000262713.7 | |
AJUBA | NM_198086.3 | c.247C>T | p.Arg83Trp | missense_variant | 6/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AJUBA | ENST00000262713.7 | c.1498C>T | p.Arg500Trp | missense_variant | 8/8 | 1 | NM_032876.6 | P1 | |
AJUBA | ENST00000397388.7 | c.247C>T | p.Arg83Trp | missense_variant | 6/6 | 2 |
Frequencies
GnomAD3 genomes AF: 0.000118 AC: 18AN: 152190Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000724 AC: 18AN: 248448Hom.: 0 AF XY: 0.0000372 AC XY: 5AN XY: 134476
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GnomAD4 exome AF: 0.000233 AC: 340AN: 1461764Hom.: 0 Cov.: 31 AF XY: 0.000204 AC XY: 148AN XY: 727178
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GnomAD4 genome AF: 0.000118 AC: 18AN: 152308Hom.: 0 Cov.: 32 AF XY: 0.0000805 AC XY: 6AN XY: 74488
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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 | Nov 17, 2022 | The c.1498C>T (p.R500W) alteration is located in exon 8 (coding exon 8) of the AJUBA gene. This alteration results from a C to T substitution at nucleotide position 1498, causing the arginine (R) at amino acid position 500 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
Uncertain
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Uncertain
T;.;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Benign
M;.;M
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Uncertain
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
D;.;D
Vest4
MVP
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