NM_053017.5:c.671T>C

Variant names:

• chr11-3639758-A-G
• rs146749287
• NM_053017.5:c.671T>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_053017.5(ART5):​c.671T>C​(p.Ile224Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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: ART5 NM_053017.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.69

Genes affected

ART5 (HGNC:24049): (ADP-ribosyltransferase 5) The protein encoded by this gene belongs to the ARG-specific ADP-ribosyltransferase family. Proteins in this family regulate the function of target proteins by attaching ADP-ribose to specific amino acid residues in their target proteins. The mouse homolog lacks a glycosylphosphatidylinositol-anchor signal sequence and is predicted to be a secretory enzyme. Several transcripts encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.867

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ART5	NM_053017.5	c.671T>C	p.Ile224Thr	missense_variant	Exon 2 of 4	ENST00000397068.8	NP_443750.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ART5	ENST00000397068.8	c.671T>C	p.Ile224Thr	missense_variant	Exon 2 of 4	1	NM_053017.5	ENSP00000380258.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Pathogenic	26
DANN	Uncertain	0.98
DEOGEN2	Benign	0.25	T;T;.
Eigen	Pathogenic	0.94
Eigen_PC	Pathogenic	0.90
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.85	.;D;D
M_CAP	Benign	0.048	D
MetaRNN	Pathogenic	0.87	D;D;D
MetaSVM	Benign	-0.61	T
MutationAssessor	Pathogenic	3.8	H;H;.
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-3.9	D;D;D
REVEL	Uncertain	0.58
Sift	Uncertain	0.0010	D;D;D
Sift4G	Uncertain	0.0030	D;D;.
Polyphen		0.99	D;D;.
Vest4		0.85
MutPred		0.77		Loss of stability (P = 0.0076);Loss of stability (P = 0.0076);.;
MVP		0.66
MPC		0.32
ClinPred		0.99	D
GERP RS		6.2
Varity_R		0.67
gMVP		0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs146749287; hg19: chr11-3660988;