4-76075909-A-C

Position:

• chr4-76075909-A-C

Variant summary

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

The NM_001130016.3(ART3):​c.20A>C​(p.Glu7Ala) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ART3 NM_001130016.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.63

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=0.1749556).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ART3	NM_001130016.3	c.20A>C	p.Glu7Ala	missense_variant	2/12	ENST00000355810.9	NP_001123488.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ART3	ENST00000355810.9	c.20A>C	p.Glu7Ala	missense_variant	2/12	1	NM_001130016.3	ENSP00000348064	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Jan 17, 2024

The c.20A>C (p.E7A) alteration is located in exon 2 (coding exon 1) of the ART3 gene. This alteration results from a A to C substitution at nucleotide position 20, causing the glutamic acid (E) at amino acid position 7 to be replaced by an alanine (A). 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	Benign	0.18
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.026	T;.;T;T;T;.;.
Eigen	Benign	-0.0027
Eigen_PC	Benign	0.029
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.79	T;T;T;T;T;T;T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.17	T;T;T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.3	.;M;.;.;M;M;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.9	N;N;N;N;N;N;N
REVEL	Benign	0.083
Sift	Uncertain	0.0060	D;D;D;D;D;D;D
Sift4G	Uncertain	0.042	D;T;T;D;T;T;T
Polyphen		0.26, 0.67, 0.62	.;B;.;.;P;P;.
Vest4		0.45, 0.43, 0.44
MutPred		0.53		Loss of disorder (P = 0.0756);Loss of disorder (P = 0.0756);Loss of disorder (P = 0.0756);Loss of disorder (P = 0.0756);Loss of disorder (P = 0.0756);Loss of disorder (P = 0.0756);Loss of disorder (P = 0.0756);
MVP		0.49
MPC		0.095
ClinPred		0.34	T
GERP RS		2.4
Varity_R		0.092
gMVP		0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr4-76997062;