chr11-3638763-G-T

Variant names:

• chr11-3638763-G-T
• rs2271586
• NM_053017.5:c.851C>A

Variant summary

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

The ENST00000397068.8(ART5):​c.851C>A​(p.Thr284Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 1,613,802 control chromosomes in the GnomAD database, including 42,223 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.29 (8394 hom., cov: 31)
  • Exomes 𝑓: 0.21 (33829 hom.)
• Consequence: ART5 ENST00000397068.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.778
• Publications: 21 publications found

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

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

• BP4: Computational evidence support a benign effect (MetaRNN=9.080657E-5).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000397068.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ART5	NM_053017.5	MANE Select	c.851C>A	p.Thr284Lys	missense	Exon 4 of 4	NP_443750.2
	ART5	NM_001079536.2		c.851C>A	p.Thr284Lys	missense	Exon 5 of 5	NP_001073004.1
	ART5	NR_123732.2		n.420C>A		non_coding_transcript_exon	Exon 4 of 4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ART5	ENST00000397068.8	TSL:1 MANE Select	c.851C>A	p.Thr284Lys	missense	Exon 4 of 4	ENSP00000380258.3
	ART5	ENST00000359918.8	TSL:1	c.851C>A	p.Thr284Lys	missense	Exon 5 of 5	ENSP00000352992.4
	ART5	ENST00000397067.7	TSL:1	c.*53C>A		3_prime_UTR	Exon 4 of 4	ENSP00000380257.3

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44724 AN: 151842 Hom.: 8364 Cov.: 31

Gnomad AFR AF: 0.541

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.261

GnomAD2 exomes AF: 0.218 AC: 54792 AN: 251422 AF XY: 0.211

Gnomad AFR exome AF: 0.544

Gnomad AMR exome AF: 0.190

Gnomad ASJ exome AF: 0.188

Gnomad EAS exome AF: 0.240

Gnomad FIN exome AF: 0.183

Gnomad NFE exome AF: 0.194

Gnomad OTH exome AF: 0.197

GnomAD4 exome AF: 0.207 AC: 302327 AN: 1461844 Hom.: 33829 Cov.: 34 AF XY: 0.206 AC XY: 149468 AN XY: 727230

African (AFR) AF: 0.554 AC: 18557 AN: 33480

American (AMR) AF: 0.189 AC: 8464 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 4879 AN: 26136

East Asian (EAS) AF: 0.262 AC: 10410 AN: 39698

South Asian (SAS) AF: 0.192 AC: 16540 AN: 86254

European-Finnish (FIN) AF: 0.181 AC: 9664 AN: 53418

Middle Eastern (MID) AF: 0.195 AC: 1124 AN: 5768

European-Non Finnish (NFE) AF: 0.197 AC: 219583 AN: 1111972

Other (OTH) AF: 0.217 AC: 13106 AN: 60394

GnomAD4 genome AF: 0.295 AC: 44810 AN: 151958 Hom.: 8394 Cov.: 31 AF XY: 0.292 AC XY: 21683 AN XY: 74250

African (AFR) AF: 0.542 AC: 22453 AN: 41430

American (AMR) AF: 0.218 AC: 3333 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 628 AN: 3464

East Asian (EAS) AF: 0.229 AC: 1172 AN: 5122

South Asian (SAS) AF: 0.186 AC: 896 AN: 4818

European-Finnish (FIN) AF: 0.191 AC: 2021 AN: 10566

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.200 AC: 13564 AN: 67974

Other (OTH) AF: 0.261 AC: 550 AN: 2108

Alfa AF: 0.217 Hom.: 19182

Bravo AF: 0.309

TwinsUK AF: 0.196 AC: 726

ALSPAC AF: 0.203 AC: 782

ESP6500AA AF: 0.525 AC: 2312

ESP6500EA AF: 0.198 AC: 1698

ExAC AF: 0.224 AC: 27155

Asia WGS AF: 0.225 AC: 781 AN: 3478

EpiCase AF: 0.192

EpiControl AF: 0.201

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	6.9
DANN	Benign	0.60
DEOGEN2	Benign	0.011	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.00022	N
LIST_S2	Benign	0.23	T
MetaRNN	Benign	0.000091	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-1.5	N
PhyloP100		0.78
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.10	N
REVEL	Benign	0.051
Sift	Benign	0.39	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.036
MPC		0.048
ClinPred		0.0056	T
GERP RS		2.8
Varity_R		0.030
gMVP		0.24
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: rs2271586; hg19: chr11-3659993; COSMIC: COSV63364223; COSMIC: COSV63364223;