Genetic Variant NM_021071.4:c.145G>T (chr12-14841153-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_021071.4(ART4):c.145G>T(p.Val49Phe) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000707 in 1,415,166 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V49I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

ART4
NM_021071.4 missense, splice_region

Scores

Splicing: ADA: 0.5183

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.39

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.144665).

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.145G>T	p.Val49Phe	missense splice_region	Exon 2 of 3	NP_066549.2	Q93070
	ART4	NM_001354646.2		c.145G>T	p.Val49Phe	missense splice_region	Exon 2 of 2	NP_001341575.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ART4	ENST00000228936.6	TSL:1 MANE Select	c.145G>T	p.Val49Phe	missense splice_region	Exon 2 of 3	ENSP00000228936.4	Q93070
ART4	ENST00000420600.2	TSL:1	c.94G>T	p.Val32Phe	missense splice_region	Exon 2 of 2	ENSP00000405689.1	H7C2G2
ART4	ENST00000430129.6	TSL:1	c.94G>T	p.Val32Phe	missense splice_region	Exon 2 of 3	ENSP00000412735.2	Q3KZ30

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.07e-7

AC:

AN:

1415166

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

701890

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30864

American (AMR)

AF:

0.00

AC:

AN:

32000

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23178

East Asian (EAS)

AF:

0.00

AC:

AN:

39342

South Asian (SAS)

AF:

0.00

AC:

AN:

78864

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51936

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5534

European-Non Finnish (NFE)

AF:

9.13e-7

AC:

AN:

1095238

Other (OTH)

AF:

0.00

AC:

AN:

58210

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.13

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.44

M_CAP

Benign

0.0070

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.0

PhyloP100

1.4

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.6

REVEL

Benign

0.088

Sift

Benign

0.031

Sift4G

Benign

0.22

Vest4

0.18

MutPred

0.26

Gain of sheet (P = 0.1208)

MVP

0.31

MPC

0.010

ClinPred

0.11

GERP RS

3.5

gMVP

0.27

Mutation Taster

=80/20

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.52

dbscSNV1_RF

Benign

0.50

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over