Variant 20-14085630-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001351661.2(MACROD2):c.173C>T(p.Thr58Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 1,544,974 control chromosomes in the GnomAD database, including 38,090 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 (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.24 ( 4687 hom., cov: 31)

Exomes 𝑓: 0.22 ( 33403 hom. )

Consequence

MACROD2
NM_001351661.2 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.78

Variant links:

Genes affected

MACROD2 (HGNC:16126): (mono-ADP ribosylhydrolase 2) The protein encoded by this gene is a deacetylase involved in removing ADP-ribose from mono-ADP-ribosylated proteins. The encoded protein has been shown to translocate from the nucleus to the cytoplasm upon DNA damage. [provided by RefSeq, May 2017]

MACROD2 links:

MACROD2 (HGNC:):

MACROD2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004529327).

BP6

Variant 20-14085630-C-T is Benign according to our data. Variant chr20-14085630-C-T is described in ClinVar as [Benign]. Clinvar id is 3059666.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MACROD2	NM_001351661.2 linkuse as main transcript	c.173C>T	p.Thr58Ile	missense_variant	3/18	ENST00000684519.1	NP_001338590.1
MACROD2	NM_001351663.2 linkuse as main transcript	c.173C>T	p.Thr58Ile	missense_variant	3/18		NP_001338592.1
MACROD2	NM_080676.6 linkuse as main transcript	c.173C>T	p.Thr58Ile	missense_variant	3/17		NP_542407.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MACROD2	ENST00000684519.1 linkuse as main transcript	c.173C>T	p.Thr58Ile	missense_variant	3/18		NM_001351661.2	ENSP00000507484.1		A1Z1Q3-1

Frequencies

GnomAD3 genomes

AF:

0.244

AC:

36925

AN:

151596

Hom.:

4683

Cov.:

show subpopulations

Gnomad AFR

AF:

0.296

Gnomad AMI

AF:

0.363

Gnomad AMR

AF:

0.264

Gnomad ASJ

AF:

0.224

Gnomad EAS

AF:

0.186

Gnomad SAS

AF:

0.243

Gnomad FIN

AF:

0.195

Gnomad MID

AF:

0.242

Gnomad NFE

AF:

0.219

Gnomad OTH

AF:

0.246

GnomAD3 exomes

AF:

0.226

AC:

50612

AN:

224064

Hom.:

5956

AF XY:

0.225

AC XY:

27442

AN XY:

121848

show subpopulations

Gnomad AFR exome

AF:

0.295

Gnomad AMR exome

AF:

0.262

Gnomad ASJ exome

AF:

0.228

Gnomad EAS exome

AF:

0.175

Gnomad SAS exome

AF:

0.253

Gnomad FIN exome

AF:

0.195

Gnomad NFE exome

AF:

0.214

Gnomad OTH exome

AF:

0.227

GnomAD4 exome

AF:

0.215

AC:

299811

AN:

1393262

Hom.:

33403

Cov.:

AF XY:

0.217

AC XY:

150098

AN XY:

692446

show subpopulations

Gnomad4 AFR exome

AF:

0.295

Gnomad4 AMR exome

AF:

0.264

Gnomad4 ASJ exome

AF:

0.226

Gnomad4 EAS exome

AF:

0.189

Gnomad4 SAS exome

AF:

0.252

Gnomad4 FIN exome

AF:

0.192

Gnomad4 NFE exome

AF:

0.210

Gnomad4 OTH exome

AF:

0.223

GnomAD4 genome

AF:

0.244

AC:

36954

AN:

151712

Hom.:

4687

Cov.:

AF XY:

0.242

AC XY:

17966

AN XY:

74126

show subpopulations

Gnomad4 AFR

AF:

0.296

Gnomad4 AMR

AF:

0.264

Gnomad4 ASJ

AF:

0.224

Gnomad4 EAS

AF:

0.186

Gnomad4 SAS

AF:

0.244

Gnomad4 FIN

AF:

0.195

Gnomad4 NFE

AF:

0.219

Gnomad4 OTH

AF:

0.245

Alfa

AF:

0.222

Hom.:

8020

Bravo

AF:

0.249

TwinsUK

AF:

0.201

AC:

746

ALSPAC

AF:

0.206

AC:

794

ESP6500AA

AF:

0.295

AC:

1061

ESP6500EA

AF:

0.210

AC:

1704

ExAC

AF:

0.227

AC:

27392

Asia WGS

AF:

0.208

AC:

718

AN:

3458

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MACROD2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 18, 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

0.078

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.017

T;.

Eigen

Benign

0.021

Eigen_PC

Benign

0.20

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.58

T;T

MetaRNN

Benign

0.0045

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

L;.

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.78

N;.

REVEL

Benign

0.085

Sift

Benign

0.10

T;.

Sift4G

Benign

0.40

T;.

Polyphen

0.099

B;.

Vest4

0.065

MPC

0.24

ClinPred

0.0057

GERP RS

4.8

Varity_R

0.19

gMVP

0.32

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