11-3659877-G-C

Position:

• chr11-3659877-G-C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_004314.3(ART1):​c.358G>C​(p.Ala120Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ART1 NM_004314.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.21

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.965

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ART1	NM_004314.3	c.358G>C	p.Ala120Pro	missense_variant	3/5	ENST00000250693.2	NP_004305.2
ART1	XM_011520114.4	c.358G>C	p.Ala120Pro	missense_variant	4/6		XP_011518416.1
ART1	XM_017017763.3	c.358G>C	p.Ala120Pro	missense_variant	4/6		XP_016873252.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ART1	ENST00000250693.2	c.358G>C	p.Ala120Pro	missense_variant	3/5	1	NM_004314.3	ENSP00000250693.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 20, 2024

The c.358G>C (p.A120P) alteration is located in exon 3 (coding exon 2) of the ART1 gene. This alteration results from a G to C substitution at nucleotide position 358, causing the alanine (A) at amino acid position 120 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.017	T
MetaRNN	Pathogenic	0.97	D
MetaSVM	Benign	-0.84	T
MutationAssessor	Pathogenic	3.8	H
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-3.7	D
REVEL	Uncertain	0.34
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.039	D
Polyphen		1.0	D
Vest4		0.92
MutPred		0.90		Gain of sheet (P = 0.039);
MVP		0.35
MPC		0.21
ClinPred		1.0	D
GERP RS		5.5
Varity_R		0.98
gMVP		0.87

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-3681107;