3-138239500-G-A
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001363941.2(ARMC8):c.809G>A(p.Arg270Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000169 in 1,598,006 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 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000017 ( 0 hom. )
Consequence
ARMC8
NM_001363941.2 missense
NM_001363941.2 missense
Scores
4
15
Clinical Significance
Conservation
PhyloP100: 3.94
Genes affected
ARMC8 (HGNC:24999): (armadillo repeat containing 8) Predicted to be involved in proteasome-mediated ubiquitin-dependent protein catabolic process. Located in cytosol and nucleoplasm. Part of ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.096850485).
BS2
High AC in GnomAdExome4 at 25 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ARMC8 | NM_001363941.2 | c.809G>A | p.Arg270Gln | missense_variant | 10/22 | ENST00000469044.6 | NP_001350870.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 151028Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000329 AC: 8AN: 242912Hom.: 0 AF XY: 0.0000456 AC XY: 6AN XY: 131470
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GnomAD4 exome AF: 0.0000173 AC: 25AN: 1446862Hom.: 0 Cov.: 28 AF XY: 0.0000250 AC XY: 18AN XY: 719094
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GnomAD4 genome AF: 0.0000132 AC: 2AN: 151144Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 73904
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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 | Mar 20, 2023 | The c.767G>A (p.R256Q) alteration is located in exon 11 (coding exon 10) of the ARMC8 gene. This alteration results from a G to A substitution at nucleotide position 767, causing the arginine (R) at amino acid position 256 to be replaced by a glutamine (Q). 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
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;.;D;D;D;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;.;L;.;.;.;L;.;.;.;.
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;N;N;N;N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;T;T;T;T;T;T;T;T
Sift4G
Benign
T;T;T;T;T;T;T;T;T;T;T
Polyphen
0.0060, 0.029, 0.027, 0.0, 0.0090
.;B;B;.;B;.;.;B;B;B;.
Vest4
MVP
MPC
0.73
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at