NM_001352754.2:c.8A>C

Variant names:

• chr2-231206246-A-C
• NM_001352754.2:c.8A>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001352754.2(ARMC9):​c.8A>C​(p.Asp3Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,456 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ARMC9 NM_001352754.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.55

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARMC9	NM_001352754.2	c.8A>C	p.Asp3Ala	missense_variant	Exon 2 of 25	ENST00000611582.5	NP_001339683.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARMC9	ENST00000611582.5	c.8A>C	p.Asp3Ala	missense_variant	Exon 2 of 25	5	NM_001352754.2	ENSP00000484804.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461456 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727058

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.35	.;T;T;T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.86	D;D;D;.
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.47	T;T;T;T
MetaSVM	Benign	-0.58	T
MutationAssessor	Pathogenic	3.1	.;M;.;M
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-3.3	D;.;D;.
REVEL	Benign	0.27
Sift	Uncertain	0.0060	D;.;D;.
Sift4G	Uncertain	0.012	D;D;D;D
Polyphen		1.0	.;D;.;D
Vest4		0.75
MutPred		0.27		Gain of catalytic residue at D3 (P = 0.0565);Gain of catalytic residue at D3 (P = 0.0565);Gain of catalytic residue at D3 (P = 0.0565);Gain of catalytic residue at D3 (P = 0.0565);
MVP		0.67
MPC		0.90
ClinPred		0.96	D
GERP RS		5.2
Varity_R		0.30
gMVP		0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-232070959;