16-31464292-TAAAAAAAAAAAAAAA-TAAAAAAAAAAAAAAAAAAA

Variant names:

• chr16-31464292-T-TAAAA
• rs537788230
• NM_001105247.2:c.1371-81_1371-78dupAAAA

Variant summary

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

The NM_001105247.2(ARMC5):​c.1371-81_1371-78dupAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000421 in 499,376 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 0.0000084 (0 hom., cov: 27)
  • Exomes 𝑓: 0.000053 (0 hom.)
• Consequence: ARMC5 NM_001105247.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• 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.1371-81_1371-78dupAAAA		intron	N/A	NP_001098717.1	Q96C12-1
	ARMC5	NM_001288767.2		c.1656-81_1656-78dupAAAA		intron	N/A	NP_001275696.1	J3KQ26
	ARMC5	NM_001301820.1		c.1467-81_1467-78dupAAAA		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.1371-102_1371-101insAAAA		intron	N/A	ENSP00000268314.4	Q96C12-1
	ARMC5	ENST00000457010.6	TSL:1	c.1371-102_1371-101insAAAA		intron	N/A	ENSP00000399561.2	Q96C12-4
	ARMC5	ENST00000408912.7	TSL:2	c.1656-102_1656-101insAAAA		intron	N/A	ENSP00000386125.3	J3KQ26

Frequencies

GnomAD3 genomes AF: 0.00000842 AC: 1 AN: 118796 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.00

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: 0.0000177

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000526 AC: 20 AN: 380580 Hom.: 0 AF XY: 0.0000260 AC XY: 5 AN XY: 192320

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

African (AFR) AF: 0.00 AC: 0 AN: 8998

American (AMR) AF: 0.000246 AC: 2 AN: 8118

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

East Asian (EAS) AF: 0.000109 AC: 2 AN: 18406

South Asian (SAS) AF: 0.0000601 AC: 1 AN: 16634

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

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

European-Non Finnish (NFE) AF: 0.0000549 AC: 15 AN: 273390

Other (OTH) AF: 0.00 AC: 0 AN: 19148

⚠️ 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: 0.00000842 AC: 1 AN: 118796 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 56774

African (AFR) AF: 0.00 AC: 0 AN: 31612

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: 0.0000177 AC: 1 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		-1.2

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;