12-14840856-G-A

Variant names:

• chr12-14840856-G-A
• rs56340844
• NM_021071.4:c.442C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_021071.4(ART4):​c.442C>T​(p.Gln148*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,862 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Affects (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (1 hom.)
• Consequence: ART4 NM_021071.4 stop_gained
• Clinical Significance: Affects no assertion criteria provided O:1
• Conservation: PhyloP100: 0.230
• Publications: 1 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ART4	NM_021071.4	MANE Select	c.442C>T	p.Gln148*	stop_gained	Exon 2 of 3	NP_066549.2
	ART4	NM_001354646.2		c.442C>T	p.Gln148*	stop_gained	Exon 2 of 2	NP_001341575.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ART4	ENST00000228936.6	TSL:1 MANE Select	c.442C>T	p.Gln148*	stop_gained	Exon 2 of 3	ENSP00000228936.4
	ART4	ENST00000420600.2	TSL:1	c.391C>T	p.Gln131*	stop_gained	Exon 2 of 2	ENSP00000405689.1
	ART4	ENST00000430129.6	TSL:1	c.165+226C>T		intron	N/A	ENSP00000412735.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461862 Hom.: 1 Cov.: 56 AF XY: 0.00000413 AC XY: 3 AN XY: 727228

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112002

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 32

ClinVar

Significance: Affects

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Blood group, Dombrock system Other:1

Jun 01, 2002

OMIM

Significance: Affects

Review Status: no assertion criteria provided

Collection Method: literature only

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.070
CADD	Pathogenic	32
DANN	Uncertain	0.99
Eigen	Benign	0.13
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.065	N
PhyloP100		0.23
Vest4		0.75
GERP RS		-0.15
Mutation Taster		=71/129	disease causing (fs/PTC)

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: rs56340844; hg19: chr12-14993790;