chr16-31459697-T-TC

Position:

• chr16-31459697-T-TC

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_001105247.2(ARMC5):​c.174dupC​(p.Glu59fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 34)
• Consequence: ARMC5 NM_001105247.2 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: -0.00200

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]

ENSG00000260267 (HGNC:):

ACMG classification

Verdict is Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 16-31459697-T-TC is Pathogenic according to our data. Variant chr16-31459697-T-TC is described in ClinVar as [Pathogenic]. Clinvar id is 1339346.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARMC5	NM_001105247.2	c.174dupC	p.Glu59fs	frameshift_variant	1/6	ENST00000268314.9	NP_001098717.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARMC5	ENST00000268314.9	c.174dupC	p.Glu59fs	frameshift_variant	1/6	5	NM_001105247.2	ENSP00000268314.4

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 34

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

clinical testing

Molecular Medicine Laboratory, University of Brescia

Sep 01, 2021

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Computational scores

Source: dbNSFP v4.3

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-31471018;