chr11-3660289-T-C

Variant names:

• chr11-3660289-T-C
• rs2280134
• NM_004314.3:c.770T>C

Variant summary

Our verdict is Benign. The variant received -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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 30 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ART1	NM_004314.3	c.770T>C	p.Leu257Pro	missense_variant	Exon 3 of 5	ENST00000250693.2	NP_004305.2
ART1	XM_011520114.4	c.770T>C	p.Leu257Pro	missense_variant	Exon 4 of 6		XP_011518416.1
ART1	XM_017017763.3	c.770T>C	p.Leu257Pro	missense_variant	Exon 4 of 6		XP_016873252.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ART1	ENST00000250693.2	c.770T>C	p.Leu257Pro	missense_variant	Exon 3 of 5	1	NM_004314.3	ENSP00000250693.1

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

GnomAD2 exomes AF: 0.654 AC: 162213 AN: 247878 AF XY: 0.650

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 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

African (AFR) AF: 0.465 AC: 15571 AN: 33480

American (AMR) AF: 0.846 AC: 37845 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.696 AC: 18181 AN: 26136

East Asian (EAS) AF: 0.381 AC: 15113 AN: 39700

South Asian (SAS) AF: 0.590 AC: 50856 AN: 86256

European-Finnish (FIN) AF: 0.675 AC: 33810 AN: 50066

Middle Eastern (MID) AF: 0.702 AC: 4051 AN: 5768

European-Non Finnish (NFE) AF: 0.672 AC: 747067 AN: 1111972

Other (OTH) AF: 0.656 AC: 39584 AN: 60372

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

African (AFR) AF: 0.479 AC: 19878 AN: 41494

American (AMR) AF: 0.794 AC: 12142 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.705 AC: 2445 AN: 3466

East Asian (EAS) AF: 0.341 AC: 1753 AN: 5148

South Asian (SAS) AF: 0.583 AC: 2806 AN: 4816

European-Finnish (FIN) AF: 0.672 AC: 7121 AN: 10598

Middle Eastern (MID) AF: 0.786 AC: 231 AN: 294

European-Non Finnish (NFE) AF: 0.677 AC: 45981 AN: 67942

Other (OTH) AF: 0.667 AC: 1407 AN: 2108

Alfa AF: 0.662 Hom.: 106956

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
PhyloP100		-0.39
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
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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