rs17001416

Variant names:

• chr4-76110646-G-T
• rs17001416
• NM_001130016.3:c.1037-1740G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001130016.3(ART3):​c.1037-1740G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 152,078 control chromosomes in the GnomAD database, including 3,028 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.16 (3028 hom., cov: 32)
• Consequence: ART3 NM_001130016.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.162
• Publications: 1 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]

NUP54 (HGNC:17359): (nucleoporin 54) The nuclear envelope creates distinct nuclear and cytoplasmic compartments in eukaryotic cells. It consists of two concentric membranes perforated by nuclear pores, large protein complexes that form aqueous channels to regulate the flow of macromolecules between the nucleus and the cytoplasm. These complexes are composed of at least 100 different polypeptide subunits, many of which belong to the nucleoporin family. This gene encodes a member of the phe-gly (FG) repeat-containing nucleoporin subset. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jun 2013]

NUP54 Gene-Disease associations (from GenCC):

• dystonia 37, early-onset, with striatal lesions

  Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ART3	NM_001130016.3	c.1037-1740G>T		intron_variant	Intron 11 of 11	ENST00000355810.9	NP_001123488.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ART3	ENST00000355810.9	c.1037-1740G>T		intron_variant	Intron 11 of 11	1	NM_001130016.3	ENSP00000348064.4

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24253 AN: 151960 Hom.: 3005 Cov.: 32

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.185

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0566

Gnomad OTH AF: 0.125

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.160 AC: 24324 AN: 152078 Hom.: 3028 Cov.: 32 AF XY: 0.164 AC XY: 12218 AN XY: 74370

African (AFR) AF: 0.338 AC: 14001 AN: 41458

American (AMR) AF: 0.167 AC: 2548 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 387 AN: 3470

East Asian (EAS) AF: 0.186 AC: 961 AN: 5172

South Asian (SAS) AF: 0.231 AC: 1116 AN: 4822

European-Finnish (FIN) AF: 0.105 AC: 1112 AN: 10586

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0566 AC: 3850 AN: 67976

Other (OTH) AF: 0.126 AC: 267 AN: 2112

Alfa AF: 0.125 Hom.: 256

Bravo AF: 0.171

Asia WGS AF: 0.258 AC: 898 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	9.0
DANN	Benign	0.84
PhyloP100		0.16
Mutation Taster		=100/0	polymorphism (auto)

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: rs17001416; hg19: chr4-77031799; COSMIC: COSV107294317; COSMIC: COSV107294317;