4-76081940-C-G

Variant summary

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

The NM_001130016.3(ART3):c.186C>G(p.Ser62Arg) 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. 15/21 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: 0.246

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=0.10648024).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ART3	NM_001130016.3	c.186C>G	p.Ser62Arg	missense_variant	3/12	ENST00000355810.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ART3	ENST00000355810.9	c.186C>G	p.Ser62Arg	missense_variant	3/12	1	NM_001130016.3	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

Mar 04, 2024

The c.186C>G (p.S62R) alteration is located in exon 3 (coding exon 2) of the ART3 gene. This alteration results from a C to G substitution at nucleotide position 186, causing the serine (S) at amino acid position 62 to be replaced by an arginine (R). 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	0.26
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
Cadd	Benign	17
Dann	Benign	0.97
DEOGEN2	Benign	0.0017	T;.;T;T;T;.;.
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.75	T;D;T;T;D;D;T
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.11	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.090	N;N;N;N;N;N;N
REVEL	Benign	0.060
Sift	Benign	0.34	T;T;T;T;T;T;T
Sift4G	Uncertain	0.042	D;T;T;D;T;T;T
Polyphen		0.57, 0.046, 0.97, 0.94, 0.88	.;P;B;.;D;P;P
Vest4		0.35, 0.33, 0.36
MutPred		0.45		Gain of MoRF binding (P = 0.0541);Gain of MoRF binding (P = 0.0541);Gain of MoRF binding (P = 0.0541);Gain of MoRF binding (P = 0.0541);Gain of MoRF binding (P = 0.0541);Gain of MoRF binding (P = 0.0541);Gain of MoRF binding (P = 0.0541);
MVP		0.30
MPC		0.22
ClinPred		0.43	T
GERP RS		2.4
Varity_R		0.10
gMVP		0.13

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: rs1722572199; hg19: chr4-77003093;