16-31464292-TAAAAAAAAAAAAAA-TAAAAAAAAAAAA

Variant names:

• chr16-31464292-TAA-T
• rs537788230
• NM_001105247.2:c.1371-79_1371-78delAA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001105247.2(ARMC5):​c.1371-79_1371-78delAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 484,612 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0017 (1 hom., cov: 27)
  • Exomes 𝑓: 0.14 (0 hom.)
• Consequence: ARMC5 NM_001105247.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.139

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 Benign. Variant got -8 ACMG points.

• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARMC5	NM_001105247.2	c.1371-79_1371-78delAA		intron_variant	Intron 3 of 5	ENST00000268314.9	NP_001098717.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARMC5	ENST00000268314.9	c.1371-101_1371-100delAA		intron_variant	Intron 3 of 5	5	NM_001105247.2	ENSP00000268314.4

Frequencies

GnomAD3 genomes AF: 0.00175 AC: 208 AN: 118778 Hom.: 1 Cov.: 27

Gnomad AFR AF: 0.000949

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00129

Gnomad ASJ AF: 0.0396

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00133

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000583

Gnomad OTH AF: 0.00190

GnomAD4 exome AF: 0.142 AC: 51868 AN: 365826 Hom.: 0 AF XY: 0.144 AC XY: 26697 AN XY: 184860

Gnomad4 AFR exome AF: 0.0966

Gnomad4 AMR exome AF: 0.179

Gnomad4 ASJ exome AF: 0.178

Gnomad4 EAS exome AF: 0.174

Gnomad4 SAS exome AF: 0.136

Gnomad4 FIN exome AF: 0.137

Gnomad4 NFE exome AF: 0.139

Gnomad4 OTH exome AF: 0.154

GnomAD4 genome AF: 0.00174 AC: 207 AN: 118786 Hom.: 1 Cov.: 27 AF XY: 0.00178 AC XY: 101 AN XY: 56774

Gnomad4 AFR AF: 0.000916

Gnomad4 AMR AF: 0.00128

Gnomad4 ASJ AF: 0.0396

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00133

Gnomad4 NFE AF: 0.000583

Gnomad4 OTH AF: 0.00190

ClinVar

Not reported in ClinVar

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

LitVar

Other links and lift over

dbSNP: rs537788230; hg19: chr16-31475613;