16-31464292-TAAAAAAAAAAAAAAA-TAAAAAAAAA

Variant names:

• chr16-31464292-TAAAAAA-T
• rs537788230
• NM_001105247.2:c.1371-83_1371-78delAAAAAA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001105247.2(ARMC5):​c.1371-83_1371-78delAAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000921 in 499,336 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000025 (0 hom., cov: 27)
  • Exomes 𝑓: 0.00011 (0 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: Uncertain_significance. The variant received 0 ACMG points.

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.1371-83_1371-78delAAAAAA		intron	N/A	NP_001098717.1	Q96C12-1
	ARMC5	NM_001288767.2		c.1656-83_1656-78delAAAAAA		intron	N/A	NP_001275696.1	J3KQ26
	ARMC5	NM_001301820.1		c.1467-83_1467-78delAAAAAA		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_1371-96delAAAAAA		intron	N/A	ENSP00000268314.4	Q96C12-1
	ARMC5	ENST00000457010.6	TSL:1	c.1371-101_1371-96delAAAAAA		intron	N/A	ENSP00000399561.2	Q96C12-4
	ARMC5	ENST00000408912.7	TSL:2	c.1656-101_1656-96delAAAAAA		intron	N/A	ENSP00000386125.3	J3KQ26

Frequencies

GnomAD3 genomes AF: 0.0000253 AC: 3 AN: 118798 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.0000949

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.000113 AC: 43 AN: 380538 Hom.: 0 AF XY: 0.0000832 AC XY: 16 AN XY: 192306

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000445 AC: 4 AN: 8996

American (AMR) AF: 0.00 AC: 0 AN: 8118

Ashkenazi Jewish (ASJ) AF: 0.000117 AC: 1 AN: 8518

East Asian (EAS) AF: 0.0000544 AC: 1 AN: 18396

South Asian (SAS) AF: 0.000240 AC: 4 AN: 16646

European-Finnish (FIN) AF: 0.0000386 AC: 1 AN: 25898

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1464

European-Non Finnish (NFE) AF: 0.0000988 AC: 27 AN: 273356

Other (OTH) AF: 0.000261 AC: 5 AN: 19146

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000253 AC: 3 AN: 118798 Hom.: 0 Cov.: 27 AF XY: 0.0000176 AC XY: 1 AN XY: 56774

African (AFR) AF: 0.0000949 AC: 3 AN: 31614

American (AMR) AF: 0.00 AC: 0 AN: 11666

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 4120

South Asian (SAS) AF: 0.00 AC: 0 AN: 3182

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 242

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 56580

Other (OTH) AF: 0.00 AC: 0 AN: 1578

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

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;