chr16-31459565-T-A

Position:

• chr16-31459565-T-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001105247.2(ARMC5):​c.41T>A​(p.Phe14Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0577 in 1,605,590 control chromosomes in the GnomAD database, including 2,984 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.045 (213 hom., cov: 33)
  • Exomes 𝑓: 0.059 (2771 hom.)
• Consequence: ARMC5 NM_001105247.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:3
• Conservation: PhyloP100: 0.781

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016966164).
• BP6: Variant 16-31459565-T-A is Benign according to our data. Variant chr16-31459565-T-A is described in ClinVar as [Benign]. Clinvar id is 1328258.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-31459565-T-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARMC5	NM_001105247.2	c.41T>A	p.Phe14Tyr	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.41T>A	p.Phe14Tyr	missense_variant	1/6	5	NM_001105247.2	ENSP00000268314.4

Frequencies

GnomAD3 genomes AF: 0.0449 AC: 6828 AN: 152114 Hom.: 213 Cov.: 33

Gnomad AFR AF: 0.0113

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.0456

Gnomad ASJ AF: 0.0701

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0263

Gnomad FIN AF: 0.0772

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0639

Gnomad OTH AF: 0.0392

GnomAD3 exomes AF: 0.0484 AC: 11339 AN: 234174 Hom.: 366 AF XY: 0.0496 AC XY: 6409 AN XY: 129124

Gnomad AFR exome AF: 0.0102

Gnomad AMR exome AF: 0.0368

Gnomad ASJ exome AF: 0.0750

Gnomad EAS exome AF: 0.000113

Gnomad SAS exome AF: 0.0299

Gnomad FIN exome AF: 0.0822

Gnomad NFE exome AF: 0.0624

Gnomad OTH exome AF: 0.0570

GnomAD4 exome AF: 0.0591 AC: 85859 AN: 1453358 Hom.: 2771 Cov.: 36 AF XY: 0.0586 AC XY: 42364 AN XY: 723166

Gnomad4 AFR exome AF: 0.0101

Gnomad4 AMR exome AF: 0.0375

Gnomad4 ASJ exome AF: 0.0732

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.0297

Gnomad4 FIN exome AF: 0.0821

Gnomad4 NFE exome AF: 0.0649

Gnomad4 OTH exome AF: 0.0537

GnomAD4 genome AF: 0.0448 AC: 6823 AN: 152232 Hom.: 213 Cov.: 33 AF XY: 0.0442 AC XY: 3291 AN XY: 74418

Gnomad4 AFR AF: 0.0113

Gnomad4 AMR AF: 0.0455

Gnomad4 ASJ AF: 0.0701

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.0264

Gnomad4 FIN AF: 0.0772

Gnomad4 NFE AF: 0.0639

Gnomad4 OTH AF: 0.0383

Alfa AF: 0.0574 Hom.: 85

Bravo AF: 0.0417

TwinsUK AF: 0.0639 AC: 237

ALSPAC AF: 0.0649 AC: 250

ESP6500AA AF: 0.0121 AC: 48

ESP6500EA AF: 0.0568 AC: 471

ExAC AF: 0.0462 AC: 5562

Asia WGS AF: 0.00924 AC: 32 AN: 3478

EpiCase AF: 0.0643

EpiControl AF: 0.0650

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:2

Benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	22
DANN	Benign	0.93
DEOGEN2	Benign	0.011	T;.;T;T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.33	T;T;.;T
MetaRNN	Benign	0.0017	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	.;N;N;N
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.10	N;N;N;N
REVEL	Benign	0.11
Sift	Benign	0.52	T;T;T;T
Sift4G	Benign	0.73	T;D;T;T
Polyphen		0.89, 0.26	.;P;B;B
Vest4		0.33
MPC		0.63
ClinPred		0.059	T
GERP RS		5.0
Varity_R		0.16
gMVP		0.26

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: rs151069962; hg19: chr16-31470886;