NM_001105247.2:c.1371-80_1371-78dupAAA

Variant names:

• chr16-31464292-T-TAAA
• rs537788230
• NM_001105247.2:c.1371-80_1371-78dupAAA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001105247.2(ARMC5):​c.1371-80_1371-78dupAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000226 in 499,262 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000017 (0 hom., cov: 27)
  • Exomes 𝑓: 0.00029 (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.

• BS1: Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.000292 (111/380458) while in subpopulation SAS AF= 0.00156 (26/16630). AF 95% confidence interval is 0.0011. There are 0 homozygotes in gnomad4_exome. There are 59 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAdExome4 at 111 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARMC5	NM_001105247.2	c.1371-80_1371-78dupAAA		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_1371-101insAAA		intron_variant	Intron 3 of 5	5	NM_001105247.2	ENSP00000268314.4

Frequencies

GnomAD3 genomes AF: 0.0000168 AC: 2 AN: 118796 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.0000316

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000857

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000292 AC: 111 AN: 380458 Hom.: 0 AF XY: 0.000307 AC XY: 59 AN XY: 192258

Gnomad4 AFR exome AF: 0.000111

Gnomad4 AMR exome AF: 0.000246

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000163

Gnomad4 SAS exome AF: 0.00156

Gnomad4 FIN exome AF: 0.0000386

Gnomad4 NFE exome AF: 0.000256

Gnomad4 OTH exome AF: 0.000418

GnomAD4 genome AF: 0.0000168 AC: 2 AN: 118804 Hom.: 0 Cov.: 27 AF XY: 0.0000176 AC XY: 1 AN XY: 56786

Gnomad4 AFR AF: 0.0000316

Gnomad4 AMR AF: 0.0000856

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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;