12-14840920-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_021071.4(ART4):c.378T>C(p.Tyr126=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 1,614,000 control chromosomes in the GnomAD database, including 103,376 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.32 (8334 hom., cov: 32)
  • Exomes 𝑓: 0.35 (95042 hom.)
• Consequence: ART4 NM_021071.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0410

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 12-14840920-A-G is Benign according to our data. Variant chr12-14840920-A-G is described in ClinVar as [Benign]. Clinvar id is 3060314.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.041 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ART4	NM_021071.4	c.378T>C	p.Tyr126=	synonymous_variant	2/3	ENST00000228936.6
ART4	NM_001354646.2	c.378T>C	p.Tyr126=	synonymous_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ART4	ENST00000228936.6	c.378T>C	p.Tyr126=	synonymous_variant	2/3	1	NM_021071.4	P1

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48784 AN: 152010 Hom.: 8322 Cov.: 32

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.0881

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.370

Gnomad OTH AF: 0.325

GnomAD3 exomes AF: 0.317 AC: 79720 AN: 251178 Hom.: 13507 AF XY: 0.321 AC XY: 43592 AN XY: 135728

Gnomad AFR exome AF: 0.272

Gnomad AMR exome AF: 0.341

Gnomad ASJ exome AF: 0.333

Gnomad EAS exome AF: 0.0849

Gnomad SAS exome AF: 0.278

Gnomad FIN exome AF: 0.263

Gnomad NFE exome AF: 0.373

Gnomad OTH exome AF: 0.334

GnomAD4 exome AF: 0.355 AC: 518609 AN: 1461872 Hom.: 95042 Cov.: 57 AF XY: 0.353 AC XY: 256863 AN XY: 727234

Gnomad4 AFR exome AF: 0.275

Gnomad4 AMR exome AF: 0.338

Gnomad4 ASJ exome AF: 0.338

Gnomad4 EAS exome AF: 0.0894

Gnomad4 SAS exome AF: 0.280

Gnomad4 FIN exome AF: 0.268

Gnomad4 NFE exome AF: 0.379

Gnomad4 OTH exome AF: 0.334

GnomAD4 genome AF: 0.321 AC: 48816 AN: 152128 Hom.: 8334 Cov.: 32 AF XY: 0.315 AC XY: 23446 AN XY: 74360

Gnomad4 AFR AF: 0.272

Gnomad4 AMR AF: 0.351

Gnomad4 ASJ AF: 0.346

Gnomad4 EAS AF: 0.0880

Gnomad4 SAS AF: 0.265

Gnomad4 FIN AF: 0.266

Gnomad4 NFE AF: 0.370

Gnomad4 OTH AF: 0.325

Alfa AF: 0.354 Hom.: 10279

Bravo AF: 0.327

Asia WGS AF: 0.180 AC: 628 AN: 3478

EpiCase AF: 0.374

EpiControl AF: 0.385

ClinVar

Significance: Benign

Submissions summary: Benign: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). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	1.0
Dann	Benign	0.75

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: rs1861698; hg19: chr12-14993854; COSMIC: COSV57451395; COSMIC: COSV57451395;