dbSNP rs745962: ARMC9:c.1718-1699T>C (chr2-231294499-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001352754.2(ARMC9):c.1718-1699T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.82 in 152,414 control chromosomes in the GnomAD database, including 51,860 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.82 ( 51774 hom., cov: 31)

Exomes 𝑓: 0.79 ( 86 hom. )

Consequence

ARMC9
NM_001352754.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.150

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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.946 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARMC9	NM_001352754.2 link	c.1718-1699T>C		intron_variant	Intron 18 of 24	ENST00000611582.5	NP_001339683.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARMC9	ENST00000611582.5 link	c.1718-1699T>C		intron_variant	Intron 18 of 24	5	NM_001352754.2	ENSP00000484804.1		Q7Z3E5-1

Frequencies

GnomAD3 genomes

AF:

0.820

AC:

124704

AN:

152024

Hom.:

51715

Cov.:

show subpopulations

Gnomad AFR

AF:

0.954

Gnomad AMI

AF:

0.728

Gnomad AMR

AF:

0.820

Gnomad ASJ

AF:

0.748

Gnomad EAS

AF:

0.861

Gnomad SAS

AF:

0.728

Gnomad FIN

AF:

0.807

Gnomad MID

AF:

0.766

Gnomad NFE

AF:

0.750

Gnomad OTH

AF:

0.801

GnomAD4 exome

AF:

0.794

AC:

216

AN:

272

Hom.:

Cov.:

AF XY:

0.789

AC XY:

161

AN XY:

204

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AF:

0.917

AC:

AN:

South Asian (SAS)

AF:

0.250

AC:

AN:

European-Finnish (FIN)

AF:

0.833

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.802

AC:

162

AN:

202

Other (OTH)

AF:

0.800

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.527

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

AF:

0.820

AC:

124816

AN:

152142

Hom.:

51774

Cov.:

AF XY:

0.821

AC XY:

61016

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.954

AC:

39639

AN:

41542

American (AMR)

AF:

0.820

AC:

12541

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.748

AC:

2595

AN:

3470

East Asian (EAS)

AF:

0.861

AC:

4450

AN:

5166

South Asian (SAS)

AF:

0.727

AC:

3489

AN:

4796

European-Finnish (FIN)

AF:

0.807

AC:

8538

AN:

10584

Middle Eastern (MID)

AF:

0.769

AC:

226

AN:

294

European-Non Finnish (NFE)

AF:

0.750

AC:

50992

AN:

67978

Other (OTH)

AF:

0.797

AC:

1682

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1111

2222

3332

4443

5554

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

874

1748

2622

3496

4370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.778

Hom.:

65786

Bravo

AF:

0.827

Asia WGS

AF:

0.805

AC:

2800

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

3.5

(source)

DANN

Benign

0.63

PhyloP100

-0.15

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over