16-31459613-A-G

Position:

• chr16-31459613-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001105247.2(ARMC5):​c.89A>G​(p.Glu30Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000692 in 1,444,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000069 (0 hom.)
• Consequence: ARMC5 NM_001105247.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.591

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]

ENSG00000260267 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.019279033).
• BP6: Variant 16-31459613-A-G is Benign according to our data. Variant chr16-31459613-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2462469.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARMC5	NM_001105247.2	c.89A>G	p.Glu30Gly	missense_variant	1/6	ENST00000268314.9	NP_001098717.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARMC5	ENST00000268314.9	c.89A>G	p.Glu30Gly	missense_variant	1/6	5	NM_001105247.2	ENSP00000268314.4

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000692 AC: 10 AN: 1444804 Hom.: 0 Cov.: 35 AF XY: 0.00000973 AC XY: 7 AN XY: 719322

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000699

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.0000167

GnomAD4 genome Cov.: 34

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 14, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.053
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	15
DANN	Benign	0.77
DEOGEN2	Benign	0.012	T;.;T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.56	T;T;.;T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.019	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.1	.;N;N;N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.99	N;N;N;N
REVEL	Benign	0.069
Sift	Benign	0.29	T;T;T;T
Sift4G	Benign	0.43	T;T;T;T
Polyphen		0.0	.;B;B;B
Vest4		0.12
MVP		0.19
MPC		0.65
ClinPred		0.10	T
GERP RS		-1.9
Varity_R		0.048
gMVP		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1433843572; hg19: chr16-31470934; COSMIC: COSV51654480; COSMIC: COSV51654480;