Genetic Variant ART3:c.-10+12312C>T (chr4-76023632-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000341029.9(ART3):c.-10+12312C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0672 in 491,938 control chromosomes in the GnomAD database, including 1,535 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.076 ( 551 hom., cov: 32)

Exomes 𝑓: 0.063 ( 984 hom. )

Consequence

ART3
ENST00000341029.9 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.919

Publications

28 publications found

Variant links:

Genes affected

ART3 (HGNC:725): (ADP-ribosyltransferase 3 (inactive)) This gene encodes an arginine-specific ADP-ribosyltransferase. The encoded protein catalyzes a reversible reaction which modifies proteins by the addition or removal of ADP-ribose to an arginine residue to regulate the function of the modified protein. An ADP-ribosyltransferase pseudogene is located on chromosome 11. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

ART3 links:

CXCL10 (HGNC:10637): (C-X-C motif chemokine ligand 10) This antimicrobial gene encodes a chemokine of the CXC subfamily and ligand for the receptor CXCR3. Binding of this protein to CXCR3 results in pleiotropic effects, including stimulation of monocytes, natural killer and T-cell migration, and modulation of adhesion molecule expression. This gene may also be a key regulator of the 'cytokine storm' immune response to SARS-CoV-2 infection. [provided by RefSeq, Sep 2020]

CXCL10 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXCL10	NM_001565.4 link	c.-201G>A		upstream_gene_variant		ENST00000306602.3	NP_001556.2	P02778

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CXCL10	ENST00000306602.3 link	c.-201G>A		upstream_gene_variant		1	NM_001565.4	ENSP00000305651.1		P02778

Frequencies

GnomAD3 genomes

AF:

0.0762

AC:

11586

AN:

152046

Hom.:

546

Cov.:

show subpopulations

Gnomad AFR

AF:

0.122

Gnomad AMI

AF:

0.0800

Gnomad AMR

AF:

0.0907

Gnomad ASJ

AF:

0.0602

Gnomad EAS

AF:

0.0989

Gnomad SAS

AF:

0.143

Gnomad FIN

AF:

0.0559

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.0419

Gnomad OTH

AF:

0.0885

GnomAD4 exome

AF:

0.0631

AC:

21430

AN:

339774

Hom.:

984

AF XY:

0.0642

AC XY:

11272

AN XY:

175626

show subpopulations

African (AFR)

AF:

0.124

AC:

1402

AN:

11284

American (AMR)

AF:

0.0972

AC:

1475

AN:

15176

Ashkenazi Jewish (ASJ)

AF:

0.0628

AC:

707

AN:

11252

East Asian (EAS)

AF:

0.117

AC:

3484

AN:

29664

South Asian (SAS)

AF:

0.130

AC:

2240

AN:

17218

European-Finnish (FIN)

AF:

0.0592

AC:

1488

AN:

25138

Middle Eastern (MID)

AF:

0.139

AC:

436

AN:

3130

European-Non Finnish (NFE)

AF:

0.0427

AC:

8807

AN:

206072

Other (OTH)

AF:

0.0667

AC:

1391

AN:

20840

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

927

1854

2781

3708

4635

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

134

268

402

536

670

<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:

0.0763

AC:

11611

AN:

152164

Hom.:

551

Cov.:

AF XY:

0.0787

AC XY:

5857

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.122

AC:

5052

AN:

41498

American (AMR)

AF:

0.0915

AC:

1398

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0602

AC:

209

AN:

3470

East Asian (EAS)

AF:

0.0989

AC:

512

AN:

5176

South Asian (SAS)

AF:

0.144

AC:

697

AN:

4824

European-Finnish (FIN)

AF:

0.0559

AC:

592

AN:

10596

Middle Eastern (MID)

AF:

0.126

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0420

AC:

2854

AN:

67996

Other (OTH)

AF:

0.0885

AC:

187

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

544

1089

1633

2178

2722

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

272

408

544

680

<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:

0.0572

Hom.:

547

Bravo

AF:

0.0802

Asia WGS

AF:

0.124

AC:

429

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.4

(source)

DANN

Benign

0.48

PhyloP100

-0.92

PromoterAI

-0.039

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over