16-31464292-TAAAAAAAAAAAAAAA-TAAAAAAAAAAAAAAAA

Variant names:

• chr16-31464292-T-TA
• rs537788230
• NM_001105247.2:c.1371-78dupA

Variant summary

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

The NM_001105247.2(ARMC5):​c.1371-78dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0342 in 497,236 control chromosomes in the GnomAD database, including 464 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.052 (464 hom., cov: 27)
  • Exomes 𝑓: 0.029 (0 hom.)
• Consequence: ARMC5 NM_001105247.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18

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: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARMC5	NM_001105247.2	c.1371-78dupA		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.1371-102_1371-101insA		intron_variant	Intron 3 of 5	5	NM_001105247.2	ENSP00000268314.4

Frequencies

GnomAD3 genomes AF: 0.0521 AC: 6178 AN: 118510 Hom.: 461 Cov.: 27

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.0203

Gnomad ASJ AF: 0.000665

Gnomad EAS AF: 0.0294

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.00149

Gnomad MID AF: 0.00826

Gnomad NFE AF: 0.00635

Gnomad OTH AF: 0.0438

GnomAD4 exome AF: 0.0286 AC: 10829 AN: 378720 Hom.: 0 AF XY: 0.0295 AC XY: 5655 AN XY: 191374

Gnomad4 AFR exome AF: 0.0445

Gnomad4 AMR exome AF: 0.0264

Gnomad4 ASJ exome AF: 0.0202

Gnomad4 EAS exome AF: 0.0335

Gnomad4 SAS exome AF: 0.0793

Gnomad4 FIN exome AF: 0.0166

Gnomad4 NFE exome AF: 0.0261

Gnomad4 OTH exome AF: 0.0293

GnomAD4 genome AF: 0.0523 AC: 6193 AN: 118516 Hom.: 464 Cov.: 27 AF XY: 0.0528 AC XY: 2991 AN XY: 56634

Gnomad4 AFR AF: 0.154

Gnomad4 AMR AF: 0.0203

Gnomad4 ASJ AF: 0.000665

Gnomad4 EAS AF: 0.0294

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.00149

Gnomad4 NFE AF: 0.00635

Gnomad4 OTH AF: 0.0468

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;