11-3660289-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004314.3(ART1):c.770T>C(p.Leu257Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.656 in 1,610,532 control chromosomes in the GnomAD database, including 351,546 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.62 (30418 hom., cov: 32)
  • Exomes 𝑓: 0.66 (321128 hom.)
• Consequence: ART1 NM_004314.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.392

Genes affected

ART1 (HGNC:723): (ADP-ribosyltransferase 1) ADP-ribosyltransferase catalyzes the ADP-ribosylation of arginine residues in proteins. Mono-ADP-ribosylation is a posttranslational modification of proteins that is interfered with by a variety of bacterial toxins including cholera, pertussis, and heat-labile enterotoxins of E. coli. The amino acid sequence consists of predominantly hydrophobic N- and C-terminal regions, which is characteristic of glycosylphosphatidylinositol (GPI)-anchored proteins. This gene was previously designated ART2. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.0185489E-6).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.783 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ART1	NM_004314.3	c.770T>C	p.Leu257Pro	missense_variant	3/5	ENST00000250693.2
ART1	XM_011520114.4	c.770T>C	p.Leu257Pro	missense_variant	4/6
ART1	XM_017017763.3	c.770T>C	p.Leu257Pro	missense_variant	4/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ART1	ENST00000250693.2	c.770T>C	p.Leu257Pro	missense_variant	3/5	1	NM_004314.3	P1

Frequencies

GnomAD3 genomes AF: 0.621 AC: 94413 AN: 151942 Hom.: 30398 Cov.: 32

Gnomad AFR AF: 0.479

Gnomad AMI AF: 0.787

Gnomad AMR AF: 0.794

Gnomad ASJ AF: 0.705

Gnomad EAS AF: 0.341

Gnomad SAS AF: 0.583

Gnomad FIN AF: 0.672

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.670

GnomAD3 exomes AF: 0.654 AC: 162213 AN: 247878 Hom.: 55239 AF XY: 0.650 AC XY: 87440 AN XY: 134526

Gnomad AFR exome AF: 0.470

Gnomad AMR exome AF: 0.853

Gnomad ASJ exome AF: 0.697

Gnomad EAS exome AF: 0.326

Gnomad SAS exome AF: 0.592

Gnomad FIN exome AF: 0.681

Gnomad NFE exome AF: 0.679

Gnomad OTH exome AF: 0.698

GnomAD4 exome AF: 0.660 AC: 962078 AN: 1458470 Hom.: 321128 Cov.: 79 AF XY: 0.658 AC XY: 477191 AN XY: 725648

Gnomad4 AFR exome AF: 0.465

Gnomad4 AMR exome AF: 0.846

Gnomad4 ASJ exome AF: 0.696

Gnomad4 EAS exome AF: 0.381

Gnomad4 SAS exome AF: 0.590

Gnomad4 FIN exome AF: 0.675

Gnomad4 NFE exome AF: 0.672

Gnomad4 OTH exome AF: 0.656

GnomAD4 genome AF: 0.621 AC: 94480 AN: 152062 Hom.: 30418 Cov.: 32 AF XY: 0.622 AC XY: 46212 AN XY: 74308

Gnomad4 AFR AF: 0.479

Gnomad4 AMR AF: 0.794

Gnomad4 ASJ AF: 0.705

Gnomad4 EAS AF: 0.341

Gnomad4 SAS AF: 0.583

Gnomad4 FIN AF: 0.672

Gnomad4 NFE AF: 0.677

Gnomad4 OTH AF: 0.667

Alfa AF: 0.673 Hom.: 49472

Bravo AF: 0.624

TwinsUK AF: 0.663 AC: 2460

ALSPAC AF: 0.662 AC: 2551

ESP6500AA AF: 0.476 AC: 2095

ESP6500EA AF: 0.685 AC: 5886

ExAC AF: 0.643 AC: 78045

Asia WGS AF: 0.516 AC: 1800 AN: 3478

EpiCase AF: 0.686

EpiControl AF: 0.692

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.036
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.75
Cadd	Benign	15
Dann	Uncertain	0.98
DEOGEN2	Benign	0.0066	T
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.0011	N
LIST_S2	Benign	0.13	T
MetaRNN	Benign	0.0000010	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.9	N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.47	T
PROVEAN	Benign	0.51	N
REVEL	Benign	0.070
Sift	Benign	0.27	T
Sift4G	Benign	0.20	T
Polyphen		0.0	B
Vest4		0.025
MPC		0.030
ClinPred		0.011	T
GERP RS		4.0
Varity_R		0.10
gMVP		0.59

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

Other links and lift over

dbSNP: rs2280134; hg19: chr11-3681519; COSMIC: COSV51704453; COSMIC: COSV51704453;