Genetic Variant ART4:c.144+2T>C (chr12-14842968-A-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_021071.4(ART4):c.144+2T>C variant causes a splice donor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000236 in 1,610,122 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Affects (no stars).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

ART4
NM_021071.4 splice_donor, intron

Scores

Splicing: ADA: 0.9709

Clinical Significance

Affects no assertion criteria provided O:1

Conservation

PhyloP100: 1.94

Variant links:

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]

ART4 links:

ENSG00000256339 (HGNC:):

ENSG00000256339 links:

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

C12orf60 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ART4	NM_021071.4 link	c.144+2T>C		splice_donor_variant, intron_variant	Intron 1 of 2	ENST00000228936.6	NP_066549.2	Q93070
ART4	NM_001354646.2 link	c.144+2T>C		splice_donor_variant, intron_variant	Intron 1 of 1		NP_001341575.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ART4	ENST00000228936.6 link	c.144+2T>C		splice_donor_variant, intron_variant	Intron 1 of 2	1	NM_021071.4	ENSP00000228936.4		Q93070

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000247

AC:

AN:

1457984

Hom.:

Cov.:

AF XY:

0.0000221

AC XY:

AN XY:

724982

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

AC:

AN:

33426

Gnomad4 AMR exome

AF:

0.00

AC:

AN:

44168

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

26020

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

39634

Gnomad4 SAS exome

AF:

0.0000117

AC:

AN:

85682

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

53234

Gnomad4 NFE exome

AF:

0.0000288

AC:

AN:

1110330

Gnomad4 Remaining exome

AF:

0.0000332

AC:

AN:

60236

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152138

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.0000241

AC:

0.0000241429

AN:

0.0000241429

Gnomad4 AMR

AF:

0.00

AC:

AN:

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00

AC:

AN:

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.0000147

AC:

0.0000147033

AN:

0.0000147033

Gnomad4 OTH

AF:

0.00

AC:

AN:

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000113

ClinVar

Significance: Affects

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Uncertain

0.084

BayesDel_noAF

Benign

-0.12

CADD

Benign

DANN

Benign

0.94

Eigen

Pathogenic

0.74

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Uncertain

0.78

GERP RS

4.3

Mutation Taster

=34/66

disease causing

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.97

dbscSNV1_RF

Benign

0.59

SpliceAI score (max)

0.97

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.97

Position offset: 2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over