rs369721476

Variant names:

• chr16-31462346-C-G
• rs369721476
• NM_001105247.2:c.799C>G

Your query was ambiguous. Multiple possible variants found:

• chr16-31462346-C-G
• chr16-31462346-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001105247.2(ARMC5):​c.799C>G​(p.Arg267Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,230 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: 0.0000014 (0 hom.)
• Consequence: ARMC5 NM_001105247.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.48
• Publications: 0 publications found

Genes affected

ARMC5 (HGNC:25781): (armadillo repeat containing 5) This gene encodes a member of the ARM (armadillo/beta-catenin-like repeat) superfamily. The ARM repeat is a tandemly repeated sequence motif with approximately 40 amino acid long. This repeat is implicated in mediating protein-protein interactions. The encoded protein contains seven ARM repeats. Mutations in this gene are associated with primary bilateral macronodular adrenal hyperplasia, which is also known as ACTH-independent macronodular adrenal hyperplasia 2. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2014]

ARMC5 Gene-Disease associations (from GenCC):

• ACTH-independent macronodular adrenal hyperplasia 2

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics
• Cushing syndrome due to macronodular adrenal hyperplasia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001105247.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARMC5	NM_001105247.2	MANE Select	c.799C>G	p.Arg267Gly	missense	Exon 3 of 6	NP_001098717.1
	ARMC5	NM_001288767.2		c.1084C>G	p.Arg362Gly	missense	Exon 5 of 8	NP_001275696.1
	ARMC5	NM_001301820.1		c.895C>G	p.Arg299Gly	missense	Exon 4 of 7	NP_001288749.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARMC5	ENST00000268314.9	TSL:5 MANE Select	c.799C>G	p.Arg267Gly	missense	Exon 3 of 6	ENSP00000268314.4
	ARMC5	ENST00000457010.6	TSL:1	c.799C>G	p.Arg267Gly	missense	Exon 3 of 4	ENSP00000399561.2
	ARMC5	ENST00000408912.7	TSL:2	c.1084C>G	p.Arg362Gly	missense	Exon 5 of 8	ENSP00000386125.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1458230 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 725226

African (AFR) AF: 0.00 AC: 0 AN: 33454

American (AMR) AF: 0.00 AC: 0 AN: 44664

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26066

East Asian (EAS) AF: 0.00 AC: 0 AN: 39638

South Asian (SAS) AF: 0.00 AC: 0 AN: 86168

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51432

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1110798

Other (OTH) AF: 0.00 AC: 0 AN: 60248

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Uncertain	0.080	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.81	T
M_CAP	Uncertain	0.17	D
MetaRNN	Uncertain	0.66	D
MetaSVM	Benign	-0.78	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		1.5
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.26
Sift	Benign	0.033	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.64
MVP		0.68
MPC		1.7
ClinPred		0.99	D
GERP RS		3.5
Varity_R		0.43
gMVP		0.43
Mutation Taster		=79/21	polymorphism

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

Other links and lift over

dbSNP: rs369721476; hg19: chr16-31473667;