chr4-76075929-G-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A14S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ART3 NM_001130016.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.21
• 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: Uncertain_significance. The variant received 0 ACMG points.

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

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.40G>A	p.Ala14Thr	missense	Exon 2 of 12	NP_001123488.1	Q13508-1
	ART3	NM_001377173.1		c.40G>A	p.Ala14Thr	missense	Exon 2 of 13	NP_001364102.1	H0Y8V6
	ART3	NM_001437636.1		c.40G>A	p.Ala14Thr	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.40G>A	p.Ala14Thr	missense	Exon 2 of 12	ENSP00000348064.4	Q13508-1
	ART3	ENST00000511188.2	TSL:1	c.40G>A	p.Ala14Thr	missense	Exon 2 of 13	ENSP00000422249.2	H0Y8V6
	ART3	ENST00000349321.7	TSL:1	c.40G>A	p.Ala14Thr	missense	Exon 2 of 11	ENSP00000304313.5	Q13508-3

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 v4.9

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
Eigen	Benign	0.029
Eigen_PC	Benign	0.033
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	1.6	L
PhyloP100		1.2
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.060
Sift	Benign	0.11	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.080	B
Vest4		0.37
MutPred		0.39		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
Mutation Taster		=85/15	polymorphism

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

Other links and lift over

dbSNP: rs776853474; hg19: chr4-76997082;