2-231282066-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 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). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P520S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

ARMC9
NM_001352754.2 missense

Scores

Clinical Significance

Pathogenic/Likely pathogenic no assertion criteria provided P:3

Conservation

PhyloP100: 4.37

Publications

3 publications found

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]

ARMC9 Gene-Disease associations (from GenCC):

Joubert syndrome 30
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen
Joubert syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ARMC9 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 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 Pathogenic/Likely_pathogenic. ClinVar VariationId is 427936.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARMC9	NM_001352754.2 link	c.1559C>T	p.Pro520Leu	missense_variant	Exon 17 of 25	ENST00000611582.5	NP_001339683.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARMC9	ENST00000611582.5 link	c.1559C>T	p.Pro520Leu	missense_variant	Exon 17 of 25	5	NM_001352754.2	ENSP00000484804.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251422

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461754

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727174

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.0000580

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000360

AC:

AN:

1111908

Other (OTH)

AF:

0.0000166

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000468

Hom.:

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

May 01, 2017

UW Hindbrain Malformation Research Program, University of Washington

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:research

- -

Joubert syndrome 30

Pathogenic:1

May 27, 2021

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Joubert syndrome

Pathogenic:1

University of Washington Center for Mendelian Genomics, University of Washington

Significance:Likely pathogenic

Review Status:no assertion criteria provided

Collection Method:research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.47

BayesDel_addAF

Benign

-0.030

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.48

.;T;T

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.95

D;D;.

M_CAP

Benign

0.024

MetaRNN

Uncertain

0.61

D;D;D

MetaSVM

Benign

-0.82

MutationAssessor

Uncertain

2.3

.;M;M

PhyloP100

4.4

PrimateAI

Uncertain

0.74

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

GERP RS

4.6

Varity_R

0.18

gMVP

0.58

Mutation Taster

=31/69

disease causing (ClinVar)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over