Variant 12-14840505-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_021071.4(ART4):c.793G>A(p.Asp265Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 1,613,718 control chromosomes in the GnomAD database, including 116,052 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,Affects (no stars).

Frequency

Genomes: 𝑓 0.34 ( 9319 hom., cov: 32)

Exomes 𝑓: 0.38 ( 106733 hom. )

Consequence

ART4
NM_021071.4 missense

Scores

Clinical Significance

Benign; Affects no assertion criteria provided B:1O:1

Conservation

PhyloP100: 0.304

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=0.0048785806).

BP6

Variant 12-14840505-C-T is Benign according to our data. Variant chr12-14840505-C-T is described in ClinVar as [Benign, Affects]. Clinvar id is 17730.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ART4	NM_021071.4 linkuse as main transcript	c.793G>A	p.Asp265Asn	missense_variant	2/3	ENST00000228936.6	NP_066549.2
ART4	NM_001354646.2 linkuse as main transcript	c.793G>A	p.Asp265Asn	missense_variant	2/2		NP_001341575.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ART4	ENST00000228936.6 linkuse as main transcript	c.793G>A	p.Asp265Asn	missense_variant	2/3	1	NM_021071.4	ENSP00000228936	P1

Frequencies

GnomAD3 genomes

AF:

0.340

AC:

51617

AN:

151986

Hom.:

9304

Cov.:

show subpopulations

Gnomad AFR

AF:

0.277

Gnomad AMI

AF:

0.524

Gnomad AMR

AF:

0.374

Gnomad ASJ

AF:

0.372

Gnomad EAS

AF:

0.0990

Gnomad SAS

AF:

0.383

Gnomad FIN

AF:

0.300

Gnomad MID

AF:

0.398

Gnomad NFE

AF:

0.386

Gnomad OTH

AF:

0.354

GnomAD3 exomes

AF:

0.347

AC:

87154

AN:

250948

Hom.:

16031

AF XY:

0.356

AC XY:

48303

AN XY:

135632

show subpopulations

Gnomad AFR exome

AF:

0.275

Gnomad AMR exome

AF:

0.354

Gnomad ASJ exome

AF:

0.358

Gnomad EAS exome

AF:

0.0977

Gnomad SAS exome

AF:

0.395

Gnomad FIN exome

AF:

0.297

Gnomad NFE exome

AF:

0.391

Gnomad OTH exome

AF:

0.367

GnomAD4 exome

AF:

0.377

AC:

550919

AN:

1461614

Hom.:

106733

Cov.:

AF XY:

0.378

AC XY:

275167

AN XY:

727100

show subpopulations

Gnomad4 AFR exome

AF:

0.274

Gnomad4 AMR exome

AF:

0.352

Gnomad4 ASJ exome

AF:

0.362

Gnomad4 EAS exome

AF:

0.102

Gnomad4 SAS exome

AF:

0.394

Gnomad4 FIN exome

AF:

0.301

Gnomad4 NFE exome

AF:

0.394

Gnomad4 OTH exome

AF:

0.360

GnomAD4 genome

AF:

0.340

AC:

51642

AN:

152104

Hom.:

9319

Cov.:

AF XY:

0.336

AC XY:

25000

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.277

Gnomad4 AMR

AF:

0.374

Gnomad4 ASJ

AF:

0.372

Gnomad4 EAS

AF:

0.0987

Gnomad4 SAS

AF:

0.384

Gnomad4 FIN

AF:

0.300

Gnomad4 NFE

AF:

0.386

Gnomad4 OTH

AF:

0.356

Alfa

AF:

0.373

Hom.:

20708

Bravo

AF:

0.341

TwinsUK

AF:

0.394

AC:

1461

ALSPAC

AF:

0.403

AC:

1554

ESP6500AA

AF:

0.279

AC:

1230

ESP6500EA

AF:

0.395

AC:

3400

ExAC

AF:

0.348

AC:

42316

Asia WGS

AF:

0.244

AC:

853

AN:

3478

EpiCase

AF:

0.395

EpiControl

AF:

0.403

ClinVar

Significance: Benign; Affects

Submissions summary: Benign:1Other: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 17, 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). -

Blood group, Dombrock system

Other:1

Affects, no assertion criteria provided

literature only

OMIM

Oct 01, 2000

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.85

BayesDel_noAF

Benign

-0.85

CADD

Benign

5.8

DANN

Benign

0.54

DEOGEN2

Benign

0.00058

.;T

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.17

.;T

MetaRNN

Benign

0.0049

T;T

MetaSVM

Benign

-0.93

MutationTaster

Benign

1.0

PrimateAI

Benign

0.36

PROVEAN

Benign

2.1

N;N

REVEL

Benign

0.046

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Vest4

0.023

MPC

0.0097

ClinPred

0.0029

GERP RS

1.1

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

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