rs587777659

Positions:

• chr16-31466773-C-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PP3_Moderate PP5 BS2

The NM_001105247.2(ARMC5):​c.2692C>T​(p.Arg898Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000632 in 1,425,022 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000063 (0 hom.)
• Consequence: ARMC5 NM_001105247.2 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.316

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]

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.873
• PP5: Variant 16-31466773-C-T is Pathogenic according to our data. Variant chr16-31466773-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 144053.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARMC5	NM_001105247.2	c.2692C>T	p.Arg898Trp	missense_variant	6/6	ENST00000268314.9	NP_001098717.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARMC5	ENST00000268314.9	c.2692C>T	p.Arg898Trp	missense_variant	6/6	5	NM_001105247.2	ENSP00000268314	P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000632 AC: 9 AN: 1425022 Hom.: 0 Cov.: 30 AF XY: 0.00000708 AC XY: 5 AN XY: 705854

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: 0.0000125

Gnomad4 FIN exome AF: 0.0000193

Gnomad4 NFE exome AF: 0.00000548

Gnomad4 OTH exome AF: 0.0000170

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

ACTH-independent macronodular adrenal hyperplasia 2 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jun 01, 2014

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.82
BayesDel_addAF	Uncertain	0.069	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	23
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.027	T;T;T;.
Eigen	Benign	0.15
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.90	D;.;D;D
M_CAP	Pathogenic	0.78	D
MetaRNN	Pathogenic	0.87	D;D;D;D
MetaSVM	Benign	-0.52	T
MutationAssessor	Benign	0.69	.;N;N;.
MutationTaster	Benign	0.92	D;D;D;D;D;D
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-1.9	N;N;N;.
REVEL	Pathogenic	0.69
Sift	Pathogenic	0.0	D;D;D;.
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		1.0	.;D;D;.
Vest4		0.84
MVP		0.60
MPC		1.5
ClinPred		0.57	D
GERP RS		3.1
Varity_R		0.15
gMVP		0.71

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

Other links and lift over

dbSNP: rs587777659; hg19: chr16-31478094;