4-76082107-C-T

Variant summary

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

The NM_001130016.3(ART3):​c.353C>T​(p.Ala118Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000136 in 1,614,102 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

ART3
NM_001130016.3 missense

Scores

4
9
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.90
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ART3NM_001130016.3 linkuse as main transcriptc.353C>T p.Ala118Val missense_variant 3/12 ENST00000355810.9 NP_001123488.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ART3ENST00000355810.9 linkuse as main transcriptc.353C>T p.Ala118Val missense_variant 3/121 NM_001130016.3 ENSP00000348064 A2Q13508-1

Frequencies

GnomAD3 genomes
AF:
0.0000854
AC:
13
AN:
152226
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000314
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000199
AC:
5
AN:
251308
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135876
show subpopulations
Gnomad AFR exome
AF:
0.000309
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000616
AC:
9
AN:
1461876
Hom.:
0
Cov.:
32
AF XY:
0.00000550
AC XY:
4
AN XY:
727236
show subpopulations
Gnomad4 AFR exome
AF:
0.000209
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000854
AC:
13
AN:
152226
Hom.:
0
Cov.:
32
AF XY:
0.0000538
AC XY:
4
AN XY:
74366
show subpopulations
Gnomad4 AFR
AF:
0.000314
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000330
Hom.:
0
Bravo
AF:
0.0000567
ExAC
AF:
0.0000412
AC:
5

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJun 23, 2021The c.353C>T (p.A118V) alteration is located in exon 3 (coding exon 2) of the ART3 gene. This alteration results from a C to T substitution at nucleotide position 353, causing the alanine (A) at amino acid position 118 to be replaced by a valine (V). 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
Uncertain
0.35
BayesDel_addAF
Benign
0.0073
T
BayesDel_noAF
Uncertain
0.080
CADD
Uncertain
24
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.21
.;T;T;T;.;.
Eigen
Pathogenic
0.86
Eigen_PC
Pathogenic
0.81
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.93
D;D;D;D;D;D
M_CAP
Benign
0.024
T
MetaRNN
Uncertain
0.66
D;D;D;D;D;D
MetaSVM
Benign
-0.72
T
MutationAssessor
Pathogenic
4.0
H;.;.;H;H;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Benign
0.48
T
PROVEAN
Uncertain
-3.8
D;D;D;D;D;D
REVEL
Uncertain
0.43
Sift
Uncertain
0.0020
D;D;D;D;D;D
Sift4G
Uncertain
0.016
D;D;D;D;D;D
Polyphen
1.0
D;D;.;D;D;P
Vest4
0.89
MVP
0.56
MPC
0.27
ClinPred
0.95
D
GERP RS
6.0
Varity_R
0.88
gMVP
0.49

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs779445420; hg19: chr4-77003260; API