NM_001105247.2:c.1371-82_1371-78delAAAAA

Variant names:

• chr16-31464292-TAAAAA-T
• rs537788230
• NM_001105247.2:c.1371-82_1371-78delAAAAA

Variant summary

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

The NM_001105247.2(ARMC5):​c.1371-82_1371-78delAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00065 in 380,158 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 0.0 (0 hom., cov: 27)
  • Exomes 𝑓: 0.00065 (0 hom.)
  • Failed GnomAD Quality Control
• 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.1371-82_1371-78delAAAAA		intron	N/A	NP_001098717.1	Q96C12-1
	ARMC5	NM_001288767.2		c.1656-82_1656-78delAAAAA		intron	N/A	NP_001275696.1	J3KQ26
	ARMC5	NM_001301820.1		c.1467-82_1467-78delAAAAA		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_1371-97delAAAAA		intron	N/A	ENSP00000268314.4	Q96C12-1
	ARMC5	ENST00000457010.6	TSL:1	c.1371-101_1371-97delAAAAA		intron	N/A	ENSP00000399561.2	Q96C12-4
	ARMC5	ENST00000408912.7	TSL:2	c.1656-101_1656-97delAAAAA		intron	N/A	ENSP00000386125.3	J3KQ26

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 118798 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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000650 AC: 247 AN: 380158 Hom.: 0 AF XY: 0.000609 AC XY: 117 AN XY: 192120

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

African (AFR) AF: 0.000889 AC: 8 AN: 8994

American (AMR) AF: 0.000740 AC: 6 AN: 8110

Ashkenazi Jewish (ASJ) AF: 0.000824 AC: 7 AN: 8500

East Asian (EAS) AF: 0.000707 AC: 13 AN: 18378

South Asian (SAS) AF: 0.000541 AC: 9 AN: 16632

European-Finnish (FIN) AF: 0.000580 AC: 15 AN: 25880

Middle Eastern (MID) AF: 0.000683 AC: 1 AN: 1464

European-Non Finnish (NFE) AF: 0.000637 AC: 174 AN: 273072

Other (OTH) AF: 0.000732 AC: 14 AN: 19128

⚠️ 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 Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 118798 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 56774

African (AFR) AF: 0.00 AC: 0 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;