Genetic Variant ART4:p.Gly108Val (chr12-14840975-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_021071.4(ART4):c.323G>T(p.Gly108Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00291 in 1,614,124 control chromosomes in the GnomAD database, including 118 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

Frequency

Genomes: 𝑓 0.015 ( 60 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 58 hom. )

Consequence

ART4
NM_021071.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.36

Publications

11 publications found

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:

ENSG00000256339 (HGNC:):

ENSG00000256339 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019409657).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0511 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021071.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ART4	NM_021071.4	MANE Select	c.323G>T	p.Gly108Val	missense	Exon 2 of 3	NP_066549.2	Q93070
	ART4	NM_001354646.2		c.323G>T	p.Gly108Val	missense	Exon 2 of 2	NP_001341575.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ART4	ENST00000228936.6	TSL:1 MANE Select	c.323G>T	p.Gly108Val	missense	Exon 2 of 3	ENSP00000228936.4	Q93070
ART4	ENST00000420600.2	TSL:1	c.272G>T	p.Gly91Val	missense	Exon 2 of 2	ENSP00000405689.1	H7C2G2
ART4	ENST00000430129.6	TSL:1	c.165+107G>T		intron	N/A	ENSP00000412735.2	Q3KZ30

Frequencies

GnomAD3 genomes

AF:

0.0153

AC:

2325

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0530

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000220

Gnomad OTH

AF:

0.0110

GnomAD2 exomes

AF:

0.00394

AC:

989

AN:

251170

AF XY:

0.00283

show subpopulations

Gnomad AFR exome

AF:

0.0540

Gnomad AMR exome

AF:

0.00223

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000185

Gnomad OTH exome

AF:

0.00180

GnomAD4 exome

AF:

0.00162

AC:

2367

AN:

1461884

Hom.:

Cov.:

AF XY:

0.00145

AC XY:

1052

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.0558

AC:

1868

AN:

33480

American (AMR)

AF:

0.00277

AC:

124

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0000765

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000696

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00312

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000129

AC:

144

AN:

1112006

Other (OTH)

AF:

0.00339

AC:

205

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

148

297

445

594

742

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

116

174

232

290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0153

AC:

2331

AN:

152240

Hom.:

Cov.:

AF XY:

0.0145

AC XY:

1081

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.0530

AC:

2200

AN:

41518

American (AMR)

AF:

0.00588

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000207

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000221

AC:

AN:

68024

Other (OTH)

AF:

0.0109

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

114

227

341

454

568

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00597

Hom.:

Bravo

AF:

0.0176

ESP6500AA

AF:

0.0504

AC:

222

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00507

AC:

616

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000356

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.0030

(source)

DANN

Benign

0.51

DEOGEN2

Benign

0.019

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.040

LIST_S2

Benign

0.63

MetaRNN

Benign

0.0019

MetaSVM

Benign

-1.0

PhyloP100

-1.4

PrimateAI

Benign

0.23

PROVEAN

Benign

-1.4

REVEL

Benign

0.019

Sift

Benign

0.20

Sift4G

Benign

0.23

Vest4

0.13

MVP

0.12

MPC

0.012

ClinPred

0.010

GERP RS

-8.7

gMVP

0.13

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over