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: ClinGen, Labcorp Genetics (formerly Invitae), G2P
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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001352754.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ARMC9	NM_001352754.2	MANE Select	c.1718-1699T>C	intron	N/A	NP_001339683.2	Q7Z3E5-1
ARMC9	NM_001271466.4		c.1718-1699T>C	intron	N/A	NP_001258395.2	Q7Z3E5-1
ARMC9	NM_001291656.2		c.1718-1699T>C	intron	N/A	NP_001278585.2	A0A2Q3DP09

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ARMC9	ENST00000611582.5	TSL:5 MANE Select	c.1718-1699T>C	intron	N/A	ENSP00000484804.1	Q7Z3E5-1
ARMC9	ENST00000349938.8	TSL:1	c.1718-1699T>C	intron	N/A	ENSP00000258417.5	A0A2Q3DP09
ARMC9	ENST00000958134.1		c.1718-1699T>C	intron	N/A	ENSP00000628193.1

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over