chr16-31459688-CG-C

Position:

• chr16-31459688-CG-C

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 9P and 4B. PVS1 PP5 BS2

The NM_001105247.2(ARMC5):​c.170delG​(p.Gly57fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000423 in 1,418,528 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000042 (0 hom.)
• Consequence: ARMC5 NM_001105247.2 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: -2.34

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 Uncertain_significance. Variant got 5 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PP5: Variant 16-31459688-CG-C is Pathogenic according to our data. Variant chr16-31459688-CG-C is described in ClinVar as [Pathogenic]. Clinvar id is 144056.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARMC5	NM_001105247.2	c.170delG	p.Gly57fs	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.170delG	p.Gly57fs	frameshift_variant	1/6	5	NM_001105247.2	ENSP00000268314.4

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000423 AC: 6 AN: 1418528 Hom.: 0 Cov.: 34 AF XY: 0.00000142 AC XY: 1 AN XY: 705750

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000537

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000263

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000503

Gnomad4 NFE exome AF: 9.09e-7

Gnomad4 OTH exome AF: 0.00

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

literature only

OMIM

Nov 28, 2013

- -

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: chr16-31471009;