Variant rs1626451 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001352754.2(ARMC9):c.539T>A(p.Ile180Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 1 in 152,354 control chromosomes in the GnomAD database, including 76,156 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I180E) has been classified as Benign.

Frequency

Genomes: 𝑓 1.0 ( 76156 hom., cov: 32)

Exomes 𝑓: 1.0 ( 719505 hom. )

Failed GnomAD Quality Control

Consequence

ARMC9
NM_001352754.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.35

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.538906E-7).

BP6

Variant 2-231222762-T-A is Benign according to our data. Variant chr2-231222762-T-A is described in ClinVar as [Benign]. Clinvar id is 1167999.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARMC9	NM_001352754.2 linkuse as main transcript	c.539T>A	p.Ile180Lys	missense_variant	6/25	ENST00000611582.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARMC9	ENST00000611582.5 linkuse as main transcript	c.539T>A	p.Ile180Lys	missense_variant	6/25	5	NM_001352754.2	P1	Q7Z3E5-1

Frequencies

GnomAD3 genomes

AF:

1.00

AC:

152215

AN:

152236

Hom.:

76097

Cov.:

show subpopulations

Gnomad AFR

AF:

1.00

Gnomad AMI

AF:

0.993

Gnomad AMR

AF:

1.00

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.997

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

1.00

GnomAD3 exomes

AF:

1.00

AC:

247607

AN:

247638

Hom.:

123788

AF XY:

1.00

AC XY:

133931

AN XY:

133942

show subpopulations

Gnomad AFR exome

AF:

1.00

Gnomad AMR exome

AF:

1.00

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

1.00

Gnomad OTH exome

AF:

1.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

1.00

AC:

1439215

AN:

1439420

Hom.:

719505

Cov.:

AF XY:

1.00

AC XY:

717093

AN XY:

717186

show subpopulations

Gnomad4 AFR exome

AF:

1.00

Gnomad4 AMR exome

AF:

1.00

Gnomad4 ASJ exome

AF:

1.00

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

1.00

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

1.00

Gnomad4 OTH exome

AF:

1.00

GnomAD4 genome

AF:

1.00

AC:

152333

AN:

152354

Hom.:

76156

Cov.:

AF XY:

1.00

AC XY:

74486

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

1.00

Gnomad4 AMR

AF:

1.00

Gnomad4 ASJ

AF:

1.00

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

1.00

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

1.00

Gnomad4 OTH

AF:

1.00

Alfa

AF:

0.848

Hom.:

15724

Bravo

AF:

1.00

TwinsUK

AF:

1.00

AC:

3708

ALSPAC

AF:

1.00

AC:

3854

ESP6500AA

AF:

1.00

AC:

4398

ESP6500EA

AF:

1.00

AC:

8591

ExAC

AF:

1.00

AC:

121375

Asia WGS

AF:

1.00

AC:

3478

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 03, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.043

.;T;T

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.61

T;T;.

MetaRNN

Benign

5.5e-7

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-1.8

.;N;N

MutationTaster

Benign

0.71

PrimateAI

Uncertain

0.49

PROVEAN

Benign

2.8

N;.;.

REVEL

Benign

0.14

Sift

Benign

0.12

T;.;.

Sift4G

Benign

0.29

T;T;T

Polyphen

0.0

.;B;B

Vest4

0.11

MPC

0.38

ClinPred

0.046

GERP RS

5.6

Varity_R

0.096

gMVP

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over