12-14840505-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate 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. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.34 (9319 hom., cov: 32)
  • Exomes 𝑓: 0.38 (106733 hom.)
• Consequence: ART4 NM_021071.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1 O:1
• Conservation: PhyloP100: 0.304

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)

ACMG classification

Verdict is Benign. Variant got -14 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]. Clinvar id is 17730.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ART4	NM_021071.4	c.793G>A	p.Asp265Asn	missense_variant	2/3	ENST00000228936.6
ART4	NM_001354646.2	c.793G>A	p.Asp265Asn	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ART4	ENST00000228936.6	c.793G>A	p.Asp265Asn	missense_variant	2/3	1	NM_021071.4	P1

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

GnomAD3 exomes AF: 0.347 AC: 87154 AN: 250948 Hom.: 16031 AF XY: 0.356 AC XY: 48303 AN XY: 135632

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 SAS exome AF: 0.395

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

Gnomad4 AFR exome AF: 0.274

Gnomad4 AMR exome AF: 0.352

Gnomad4 ASJ exome AF: 0.362

Gnomad4 EAS exome AF: 0.102

Gnomad4 SAS exome AF: 0.394

Gnomad4 FIN exome AF: 0.301

Gnomad4 NFE exome AF: 0.394

Gnomad4 OTH exome AF: 0.360

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

Gnomad4 AFR AF: 0.277

Gnomad4 AMR AF: 0.374

Gnomad4 ASJ AF: 0.372

Gnomad4 EAS AF: 0.0987

Gnomad4 SAS AF: 0.384

Gnomad4 FIN AF: 0.300

Gnomad4 NFE AF: 0.386

Gnomad4 OTH AF: 0.356

Alfa AF: 0.373 Hom.: 20708

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

Significance: Benign

Submissions summary: Benign:1 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

ART4-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Blood group, Dombrock system Other:1

Affects, no assertion criteria provided

literature only

OMIM

Oct 01, 2000

- -

Computational scores

Source: dbNSFP v4.3

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
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.023	N
MetaRNN	Benign	0.0049	T;T
MetaSVM	Benign	-0.93	T
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.36	T
PROVEAN	Benign	2.1	N;N
REVEL	Benign	0.046
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Vest4		0.023
MPC		0.0097
ClinPred		0.0029	T
GERP RS		1.1
gMVP		0.26

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

Other links and lift over

dbSNP: rs11276; hg19: chr12-14993439; COSMIC: COSV57451379; COSMIC: COSV57451379;