NM_021071.4:c.793G>A

Variant names:

• chr12-14840505-C-T
• rs11276
• NM_021071.4:c.793G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_021071.4(ART4):​c.793G>A​(p.Asp265Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 1,613,718 control chromosomes in the GnomAD database, including 116,052 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign,Affects (no stars).

• Frequency:
  • Genomes: 𝑓 0.34 (9319 hom., cov: 32)
  • Exomes 𝑓: 0.38 (106733 hom.)
• Consequence: ART4 NM_021071.4 missense
• Clinical Significance: Benign; Affects no assertion criteria provided B:1 O:1
• Conservation: PhyloP100: 0.304
• Publications: 58 publications found

Genes affected

ART4 (HGNC:726): (ADP-ribosyltransferase 4 (inactive) (Dombrock blood group)) This gene encodes a protein that contains a mono-ADP-ribosylation (ART) motif. It is a member of the ADP-ribosyltransferase gene family but enzymatic activity has not been demonstrated experimentally. Antigens of the Dombrock blood group system are located on the gene product, which is glycosylphosphatidylinosotol-anchored to the erythrocyte membrane. Allelic variants, some of which lead to adverse transfusion reactions, are known. [provided by RefSeq, Jul 2008]

C12orf60 (HGNC:28726): (chromosome 12 open reading frame 60)

ENSG00000256339 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0048785806).
• BP6: Variant 12-14840505-C-T is Benign according to our data. Variant chr12-14840505-C-T is described in ClinVar as Benign|Affects. ClinVar VariationId is 17730.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021071.4. 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
	ART4	NM_021071.4	MANE Select	c.793G>A	p.Asp265Asn	missense	Exon 2 of 3	NP_066549.2	Q93070
	ART4	NM_001354646.2		c.793G>A	p.Asp265Asn	missense	Exon 2 of 2	NP_001341575.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ART4	ENST00000228936.6	TSL:1 MANE Select	c.793G>A	p.Asp265Asn	missense	Exon 2 of 3	ENSP00000228936.4	Q93070
	ART4	ENST00000420600.2	TSL:1	c.742G>A	p.Asp248Asn	missense	Exon 2 of 2	ENSP00000405689.1	H7C2G2
	ART4	ENST00000430129.6	TSL:1	c.165+577G>A		intron	N/A	ENSP00000412735.2	Q3KZ30

Frequencies

GnomAD3 genomes AF: 0.340 AC: 51617 AN: 151986 Hom.: 9304 Cov.: 32

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.0990

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.398

Gnomad NFE AF: 0.386

Gnomad OTH AF: 0.354

GnomAD2 exomes AF: 0.347 AC: 87154 AN: 250948 AF XY: 0.356

Gnomad AFR exome AF: 0.275

Gnomad AMR exome AF: 0.354

Gnomad ASJ exome AF: 0.358

Gnomad EAS exome AF: 0.0977

Gnomad FIN exome AF: 0.297

Gnomad NFE exome AF: 0.391

Gnomad OTH exome AF: 0.367

GnomAD4 exome AF: 0.377 AC: 550919 AN: 1461614 Hom.: 106733 Cov.: 48 AF XY: 0.378 AC XY: 275167 AN XY: 727100

African (AFR) AF: 0.274 AC: 9163 AN: 33478

American (AMR) AF: 0.352 AC: 15731 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 9451 AN: 26120

East Asian (EAS) AF: 0.102 AC: 4067 AN: 39700

South Asian (SAS) AF: 0.394 AC: 34002 AN: 86194

European-Finnish (FIN) AF: 0.301 AC: 16092 AN: 53416

Middle Eastern (MID) AF: 0.442 AC: 2543 AN: 5758

European-Non Finnish (NFE) AF: 0.394 AC: 438110 AN: 1111866

Other (OTH) AF: 0.360 AC: 21760 AN: 60386

GnomAD4 genome AF: 0.340 AC: 51642 AN: 152104 Hom.: 9319 Cov.: 32 AF XY: 0.336 AC XY: 25000 AN XY: 74384

African (AFR) AF: 0.277 AC: 11483 AN: 41478

American (AMR) AF: 0.374 AC: 5727 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.372 AC: 1289 AN: 3466

East Asian (EAS) AF: 0.0987 AC: 511 AN: 5178

South Asian (SAS) AF: 0.384 AC: 1853 AN: 4826

European-Finnish (FIN) AF: 0.300 AC: 3168 AN: 10574

Middle Eastern (MID) AF: 0.397 AC: 116 AN: 292

European-Non Finnish (NFE) AF: 0.386 AC: 26269 AN: 67978

Other (OTH) AF: 0.356 AC: 751 AN: 2112

Alfa AF: 0.368 Hom.: 26891

Bravo AF: 0.341

TwinsUK AF: 0.394 AC: 1461

ALSPAC AF: 0.403 AC: 1554

ESP6500AA AF: 0.279 AC: 1230

ESP6500EA AF: 0.395 AC: 3400

ExAC AF: 0.348 AC: 42316

Asia WGS AF: 0.244 AC: 853 AN: 3478

EpiCase AF: 0.395

EpiControl AF: 0.403

ClinVar

ClinVar submissions

Significance: Benign; Affects

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	ART4-related disorder (1)
-	-	-	Blood group, Dombrock system (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.85	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.8
DANN	Benign	0.54
DEOGEN2	Benign	0.00058	T
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.17	T
MetaRNN	Benign	0.0049	T
MetaSVM	Benign	-0.93	T
PhyloP100		0.30
PrimateAI	Benign	0.36	T
PROVEAN	Benign	2.1	N
REVEL	Benign	0.046
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Vest4		0.023
MPC		0.0097
ClinPred		0.0029	T
GERP RS		1.1
gMVP		0.26
Mutation Taster		=99/1	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: rs11276; hg19: chr12-14993439; COSMIC: COSV57451379; COSMIC: COSV57451379;