Variant 12-14829418-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_021071.4(ART4):c.898C>G(p.Leu300Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 1,606,268 control chromosomes in the GnomAD database, including 11,176 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 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 0.12 ( 1312 hom., cov: 32)

Exomes 𝑓: 0.11 ( 9864 hom. )

Consequence

ART4
NM_021071.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.332

Variant links:

Genes affected

ART4 (HGNC:726): (ADP-ribosyltransferase 4 (inactive) (Dombrock blood group)) This gene encodes a protein that contains a mono-ADP-ribosylation (ART) motif. It is a member of the ADP-ribosyltransferase gene family but enzymatic activity has not been demonstrated experimentally. Antigens of the Dombrock blood group system are located on the gene product, which is glycosylphosphatidylinosotol-anchored to the erythrocyte membrane. Allelic variants, some of which lead to adverse transfusion reactions, are known. [provided by RefSeq, Jul 2008]

ART4 links:

C12orf60 (HGNC:28726): (chromosome 12 open reading frame 60)

C12orf60 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=0.0039037168).

BP6

Variant 12-14829418-G-C is Benign according to our data. Variant chr12-14829418-G-C is described in ClinVar as [Benign]. Clinvar id is 3060827.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ART4	NM_021071.4 linkuse as main transcript	c.898C>G	p.Leu300Val	missense_variant	3/3	ENST00000228936.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ART4	ENST00000228936.6 linkuse as main transcript	c.898C>G	p.Leu300Val	missense_variant	3/3	1	NM_021071.4	P1

Frequencies

GnomAD3 genomes

AF:

0.120

AC:

18240

AN:

152010

Hom.:

1304

Cov.:

show subpopulations

Gnomad AFR

AF:

0.120

Gnomad AMI

AF:

0.0681

Gnomad AMR

AF:

0.226

Gnomad ASJ

AF:

0.0758

Gnomad EAS

AF:

0.0891

Gnomad SAS

AF:

0.0843

Gnomad FIN

AF:

0.158

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0986

Gnomad OTH

AF:

0.114

GnomAD3 exomes

AF:

0.129

AC:

32062

AN:

247736

Hom.:

3153

AF XY:

0.119

AC XY:

15911

AN XY:

134112

show subpopulations

Gnomad AFR exome

AF:

0.118

Gnomad AMR exome

AF:

0.331

Gnomad ASJ exome

AF:

0.0747

Gnomad EAS exome

AF:

0.0844

Gnomad SAS exome

AF:

0.0764

Gnomad FIN exome

AF:

0.153

Gnomad NFE exome

AF:

0.0939

Gnomad OTH exome

AF:

0.119

GnomAD4 exome

AF:

0.106

AC:

154611

AN:

1454140

Hom.:

9864

Cov.:

AF XY:

0.104

AC XY:

74862

AN XY:

723294

show subpopulations

Gnomad4 AFR exome

AF:

0.117

Gnomad4 AMR exome

AF:

0.326

Gnomad4 ASJ exome

AF:

0.0748

Gnomad4 EAS exome

AF:

0.0841

Gnomad4 SAS exome

AF:

0.0772

Gnomad4 FIN exome

AF:

0.152

Gnomad4 NFE exome

AF:

0.0995

Gnomad4 OTH exome

AF:

0.104

GnomAD4 genome

AF:

0.120

AC:

18278

AN:

152128

Hom.:

1312

Cov.:

AF XY:

0.125

AC XY:

9295

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.120

Gnomad4 AMR

AF:

0.227

Gnomad4 ASJ

AF:

0.0758

Gnomad4 EAS

AF:

0.0897

Gnomad4 SAS

AF:

0.0844

Gnomad4 FIN

AF:

0.158

Gnomad4 NFE

AF:

0.0986

Gnomad4 OTH

AF:

0.115

Alfa

AF:

0.0991

Hom.:

579

Bravo

AF:

0.129

TwinsUK

AF:

0.104

AC:

386

ALSPAC

AF:

0.102

AC:

392

ESP6500AA

AF:

0.115

AC:

508

ESP6500EA

AF:

0.0978

AC:

841

ExAC

AF:

0.123

AC:

14905

Asia WGS

AF:

0.115

AC:

399

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ART4-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 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

0.083

BayesDel_addAF

Benign

-0.85

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.20

DANN

Benign

0.76

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.022

MetaRNN

Benign

0.0039

MetaSVM

Benign

-0.94

MutationTaster

Benign

1.0

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.61

REVEL

Benign

0.0030

Sift

Benign

0.12

Sift4G

Uncertain

0.027

Vest4

0.035

MPC

0.0097

ClinPred

0.0049

GERP RS

-5.7

gMVP

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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