4-76075944-G-C

Variant names:

• chr4-76075944-G-C
• rs1578428172
• NM_001130016.3:c.55G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001130016.3(ART3):​c.55G>C​(p.Val19Leu) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. V19V) has been classified 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: 0.342
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.056315154).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130016.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ART3	NM_001130016.3	MANE Select	c.55G>C	p.Val19Leu	missense	Exon 2 of 12	NP_001123488.1	Q13508-1
	ART3	NM_001377173.1		c.55G>C	p.Val19Leu	missense	Exon 2 of 13	NP_001364102.1	H0Y8V6
	ART3	NM_001437636.1		c.55G>C	p.Val19Leu	missense	Exon 2 of 11	NP_001424565.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ART3	ENST00000355810.9	TSL:1 MANE Select	c.55G>C	p.Val19Leu	missense	Exon 2 of 12	ENSP00000348064.4	Q13508-1
	ART3	ENST00000511188.2	TSL:1	c.55G>C	p.Val19Leu	missense	Exon 2 of 13	ENSP00000422249.2	H0Y8V6
	ART3	ENST00000349321.7	TSL:1	c.55G>C	p.Val19Leu	missense	Exon 2 of 11	ENSP00000304313.5	Q13508-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	12
DANN	Benign	0.92
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.056	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.23	N
PhyloP100		0.34
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.32	N
REVEL	Benign	0.044
Sift	Benign	1.0	T
Sift4G	Benign	0.11	T
Polyphen		0.017	B
Vest4		0.34
MutPred		0.43		Loss of sheet (P = 0.0063)
MVP		0.32
MPC		0.037
ClinPred		0.053	T
GERP RS		-0.24
Varity_R		0.055
gMVP		0.17
Mutation Taster		=99/1	polymorphism

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: rs1578428172; hg19: chr4-76997097;