rs1114167449
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP5
The NM_001352754.2(ARMC9):c.1559C>T(p.Pro520Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000684 in 1,461,754 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000068 ( 0 hom. )
Consequence
ARMC9
NM_001352754.2 missense
NM_001352754.2 missense
Scores
1
12
6
Clinical Significance
Conservation
PhyloP100: 4.37
Genes affected
ARMC9 (HGNC:20730): (armadillo repeat containing 9) Predicted to be involved in cilium assembly and positive regulation of smoothened signaling pathway. Located in centriole and ciliary basal body. Implicated in Joubert syndrome 30. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 2-231282066-C-T is Pathogenic according to our data. Variant chr2-231282066-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 427936.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-231282066-C-T is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ARMC9 | NM_001352754.2 | c.1559C>T | p.Pro520Leu | missense_variant | 17/25 | ENST00000611582.5 | NP_001339683.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ARMC9 | ENST00000611582.5 | c.1559C>T | p.Pro520Leu | missense_variant | 17/25 | 5 | NM_001352754.2 | ENSP00000484804 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251422Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135870
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GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461754Hom.: 0 Cov.: 30 AF XY: 0.00000963 AC XY: 7AN XY: 727174
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GnomAD4 genome Cov.: 32
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32
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ClinVar
Significance: Pathogenic/Likely pathogenic
Submissions summary: Pathogenic:3
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
ARMC9-related Joubert syndrome Pathogenic:1
Pathogenic, no assertion criteria provided | research | UW Hindbrain Malformation Research Program, University of Washington | May 01, 2017 | - - |
Joubert syndrome 30 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | May 27, 2021 | - - |
Familial aplasia of the vermis Pathogenic:1
Likely pathogenic, no assertion criteria provided | research | University of Washington Center for Mendelian Genomics, University of Washington | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
.;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;.
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
.;M;M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;.;.
REVEL
Benign
Sift
Uncertain
D;.;.
Sift4G
Uncertain
D;D;D
Polyphen
0.98
.;D;D
Vest4
MutPred
Loss of catalytic residue at P520 (P = 0.0264);Loss of catalytic residue at P520 (P = 0.0264);Loss of catalytic residue at P520 (P = 0.0264);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
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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