16-31464292-TAAAAAAAAAAAAAAA-TAAAAAAA

Variant names:

• chr16-31464292-TAAAAAAAA-T
• rs537788230
• NM_001105247.2:c.1371-85_1371-78delAAAAAAAA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001105247.2(ARMC5):​c.1371-85_1371-78delAAAAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0131 in 499,446 control chromosomes in the GnomAD database, including 280 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.040 (264 hom., cov: 27)
  • Exomes 𝑓: 0.0048 (16 hom.)
• Consequence: ARMC5 NM_001105247.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28
• Publications: 0 publications found

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]

ARMC5 Gene-Disease associations (from GenCC):

• ACTH-independent macronodular adrenal hyperplasia 2

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp
• Cushing syndrome due to macronodular adrenal hyperplasia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001105247.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARMC5	NM_001105247.2	MANE Select	c.1371-85_1371-78delAAAAAAAA		intron	N/A	NP_001098717.1	Q96C12-1
	ARMC5	NM_001288767.2		c.1656-85_1656-78delAAAAAAAA		intron	N/A	NP_001275696.1	J3KQ26
	ARMC5	NM_001301820.1		c.1467-85_1467-78delAAAAAAAA		intron	N/A	NP_001288749.1	Q96C12

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARMC5	ENST00000268314.9	TSL:5 MANE Select	c.1371-101_1371-94delAAAAAAAA		intron	N/A	ENSP00000268314.4	Q96C12-1
	ARMC5	ENST00000457010.6	TSL:1	c.1371-101_1371-94delAAAAAAAA		intron	N/A	ENSP00000399561.2	Q96C12-4
	ARMC5	ENST00000408912.7	TSL:2	c.1656-101_1656-94delAAAAAAAA		intron	N/A	ENSP00000386125.3	J3KQ26

Frequencies

GnomAD3 genomes AF: 0.0397 AC: 4721 AN: 118836 Hom.: 264 Cov.: 27

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0149

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000942

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0124

Gnomad NFE AF: 0.000460

Gnomad OTH AF: 0.0247

GnomAD4 exome AF: 0.00481 AC: 1832 AN: 380596 Hom.: 16 AF XY: 0.00436 AC XY: 838 AN XY: 192334

African (AFR) AF: 0.157 AC: 1411 AN: 8992

American (AMR) AF: 0.0115 AC: 93 AN: 8120

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8520

East Asian (EAS) AF: 0.00 AC: 0 AN: 18406

South Asian (SAS) AF: 0.000541 AC: 9 AN: 16646

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25902

Middle Eastern (MID) AF: 0.00888 AC: 13 AN: 1464

European-Non Finnish (NFE) AF: 0.000347 AC: 95 AN: 273400

Other (OTH) AF: 0.0110 AC: 211 AN: 19146

GnomAD4 genome AF: 0.0398 AC: 4732 AN: 118850 Hom.: 264 Cov.: 27 AF XY: 0.0389 AC XY: 2211 AN XY: 56812

African (AFR) AF: 0.142 AC: 4488 AN: 31706

American (AMR) AF: 0.0149 AC: 174 AN: 11674

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3008

East Asian (EAS) AF: 0.00 AC: 0 AN: 4112

South Asian (SAS) AF: 0.000631 AC: 2 AN: 3170

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6034

Middle Eastern (MID) AF: 0.0136 AC: 3 AN: 220

European-Non Finnish (NFE) AF: 0.000460 AC: 26 AN: 56570

Other (OTH) AF: 0.0247 AC: 39 AN: 1582

Alfa AF: 0.00 Hom.: 20

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs537788230; hg19: chr16-31475613;