Variant 6-108876176-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_032131.6(ARMC2):c.497T>C(p.Met166Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0336 in 1,611,400 control chromosomes in the GnomAD database, including 2,500 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 0.032 ( 221 hom., cov: 32)

Exomes 𝑓: 0.034 ( 2279 hom. )

Consequence

ARMC2
NM_032131.6 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.14

Variant links:

Genes affected

ARMC2 (HGNC:23045): (armadillo repeat containing 2) Involved in sperm axoneme assembly. Implicated in spermatogenic failure 38. [provided by Alliance of Genome Resources, Apr 2022]

ARMC2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0042066276).

BP6

Variant 6-108876176-T-C is Benign according to our data. Variant chr6-108876176-T-C is described in ClinVar as [Benign]. Clinvar id is 3057122.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARMC2	NM_032131.6 linkuse as main transcript	c.497T>C	p.Met166Thr	missense_variant	5/18	ENST00000392644.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARMC2	ENST00000392644.9 linkuse as main transcript	c.497T>C	p.Met166Thr	missense_variant	5/18	1	NM_032131.6	P1	Q8NEN0-1
ARMC2	ENST00000368972.7 linkuse as main transcript	c.2T>C	p.Met1?	start_lost	4/17	2			Q8NEN0-2
ARMC2	ENST00000237512.4 linkuse as main transcript	c.497T>C	p.Met166Thr	missense_variant	5/5	2
ARMC2	ENST00000414610.1 linkuse as main transcript	c.53T>C	p.Met18Thr	missense_variant	2/3	5

Frequencies

GnomAD3 genomes

AF:

0.0322

AC:

4893

AN:

152164

Hom.:

220

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00982

Gnomad AMI

AF:

0.0165

Gnomad AMR

AF:

0.0417

Gnomad ASJ

AF:

0.00576

Gnomad EAS

AF:

0.210

Gnomad SAS

AF:

0.143

Gnomad FIN

AF:

0.0543

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0203

Gnomad OTH

AF:

0.0321

GnomAD3 exomes

AF:

0.0566

AC:

14077

AN:

248588

Hom.:

893

AF XY:

0.0586

AC XY:

7868

AN XY:

134330

show subpopulations

Gnomad AFR exome

AF:

0.00941

Gnomad AMR exome

AF:

0.0627

Gnomad ASJ exome

AF:

0.00659

Gnomad EAS exome

AF:

0.218

Gnomad SAS exome

AF:

0.133

Gnomad FIN exome

AF:

0.0563

Gnomad NFE exome

AF:

0.0207

Gnomad OTH exome

AF:

0.0398

GnomAD4 exome

AF:

0.0337

AC:

49234

AN:

1459118

Hom.:

2279

Cov.:

AF XY:

0.0364

AC XY:

26436

AN XY:

725680

show subpopulations

Gnomad4 AFR exome

AF:

0.00910

Gnomad4 AMR exome

AF:

0.0606

Gnomad4 ASJ exome

AF:

0.00540

Gnomad4 EAS exome

AF:

0.214

Gnomad4 SAS exome

AF:

0.130

Gnomad4 FIN exome

AF:

0.0525

Gnomad4 NFE exome

AF:

0.0191

Gnomad4 OTH exome

AF:

0.0376

GnomAD4 genome

AF:

0.0322

AC:

4905

AN:

152282

Hom.:

221

Cov.:

AF XY:

0.0372

AC XY:

2773

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.00982

Gnomad4 AMR

AF:

0.0418

Gnomad4 ASJ

AF:

0.00576

Gnomad4 EAS

AF:

0.210

Gnomad4 SAS

AF:

0.143

Gnomad4 FIN

AF:

0.0543

Gnomad4 NFE

AF:

0.0203

Gnomad4 OTH

AF:

0.0346

Alfa

AF:

0.0259

Hom.:

347

Bravo

AF:

0.0312

TwinsUK

AF:

0.0229

AC:

ALSPAC

AF:

0.0215

AC:

ESP6500AA

AF:

0.00794

AC:

ESP6500EA

AF:

0.0190

AC:

163

ExAC

AF:

0.0562

AC:

6821

Asia WGS

AF:

0.156

AC:

543

AN:

3478

EpiCase

AF:

0.0196

EpiControl

AF:

0.0205

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

ARMC2-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 11, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.58

Cadd

Benign

0.024

Dann

Benign

0.78

Eigen

Benign

-0.99

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.011

LIST_S2

Uncertain

0.90

D;T;T

MetaRNN

Benign

0.0042

T;T;T

MetaSVM

Benign

-0.99

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.10

N;N;N

REVEL

Benign

0.022

Sift

Uncertain

0.027

D;T;T

Sift4G

Uncertain

0.034

D;T;T

Polyphen

0.0

.;B;.

Vest4

0.056

MPC

0.15

ClinPred

0.0068

GERP RS

-5.0

Varity_R

0.050

gMVP

0.12

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over