NM_001130016.3:c.40G>A

Variant names:

• chr4-76075929-G-A
• rs776853474
• NM_001130016.3:c.40G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001130016.3(ART3):​c.40G>A​(p.Ala14Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: ART3 NM_001130016.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.21

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25134522).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ART3	NM_001130016.3	c.40G>A	p.Ala14Thr	missense_variant	Exon 2 of 12	ENST00000355810.9	NP_001123488.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ART3	ENST00000355810.9	c.40G>A	p.Ala14Thr	missense_variant	Exon 2 of 12	1	NM_001130016.3	ENSP00000348064.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.029	T;.;T;T;T;.;.
Eigen	Benign	0.029
Eigen_PC	Benign	0.033
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.71	T;T;T;T;T;T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.25	T;T;T;T;T;T;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	1.6	.;L;.;.;L;L;.
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.2	N;N;N;N;N;N;N
REVEL	Benign	0.060
Sift	Benign	0.11	T;D;T;T;D;D;T
Sift4G	Pathogenic	0.0	D;D;T;D;D;D;T
Polyphen		0.080, 0.97, 0.98	.;B;.;.;D;D;.
Vest4		0.37, 0.40, 0.40
MutPred		0.39		Gain of helix (P = 0.2294);Gain of helix (P = 0.2294);Gain of helix (P = 0.2294);Gain of helix (P = 0.2294);Gain of helix (P = 0.2294);Gain of helix (P = 0.2294);Gain of helix (P = 0.2294);
MVP		0.50
MPC		0.053
ClinPred		0.61	D
GERP RS		3.2
Varity_R		0.047
gMVP		0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs776853474; hg19: chr4-76997082;