rs1114167449

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

Scores

1
12
6

Clinical Significance

Pathogenic/Likely pathogenic no assertion criteria provided P:3

Conservation

PhyloP100: 4.37
Variant links:
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]

Genome browser will be placed here

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
ARMC9NM_001352754.2 linkuse as main transcriptc.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
ARMC9ENST00000611582.5 linkuse as main transcriptc.1559C>T p.Pro520Leu missense_variant 17/255 NM_001352754.2 ENSP00000484804 P1Q7Z3E5-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251422
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135870
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000684
AC:
10
AN:
1461754
Hom.:
0
Cov.:
30
AF XY:
0.00000963
AC XY:
7
AN XY:
727174
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000580
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000360
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000468
Hom.:
0

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 providedresearchUW Hindbrain Malformation Research Program, University of WashingtonMay 01, 2017- -
Joubert syndrome 30 Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMMay 27, 2021- -
Familial aplasia of the vermis Pathogenic:1
Likely pathogenic, no assertion criteria providedresearchUniversity of Washington Center for Mendelian Genomics, University of Washington-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.47
BayesDel_addAF
Benign
-0.030
T
BayesDel_noAF
Benign
-0.28
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.48
.;T;T
Eigen
Uncertain
0.56
Eigen_PC
Uncertain
0.57
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Uncertain
0.95
D;D;.
M_CAP
Benign
0.024
T
MetaRNN
Uncertain
0.61
D;D;D
MetaSVM
Benign
-0.82
T
MutationAssessor
Uncertain
2.3
.;M;M
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.74
T
PROVEAN
Pathogenic
-5.0
D;.;.
REVEL
Benign
0.15
Sift
Uncertain
0.017
D;.;.
Sift4G
Uncertain
0.038
D;D;D
Polyphen
0.98
.;D;D
Vest4
0.63
MutPred
0.43
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
0.74
MPC
0.45
ClinPred
0.98
D
GERP RS
4.6
Varity_R
0.18
gMVP
0.58

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1114167449; hg19: chr2-232146779; API