NM_021071.4:c.145G>T

Variant names:

• chr12-14841153-C-A
• NM_021071.4:c.145G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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. 14/21 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.

• 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

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]

ENSG00000256339 (HGNC:):

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

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.144665).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ART4	NM_021071.4	c.145G>T	p.Val49Phe	missense_variant, splice_region_variant	Exon 2 of 3	ENST00000228936.6	NP_066549.2
ART4	NM_001354646.2	c.145G>T	p.Val49Phe	missense_variant, splice_region_variant	Exon 2 of 2		NP_001341575.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ART4	ENST00000228936.6	c.145G>T	p.Val49Phe	missense_variant, splice_region_variant	Exon 2 of 3	1	NM_021071.4	ENSP00000228936.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.07e-7 AC: 1 AN: 1415166 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 701890

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.13e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.13	.;T;T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.44	.;T;T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.14	T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.6	N;D;N
REVEL	Benign	0.088
Sift	Benign	0.031	D;D;D
Sift4G	Benign	0.22	T;D;T
Vest4		0.18
MutPred		0.26		Gain of sheet (P = 0.1208);.;.;
MVP		0.31
MPC		0.010
ClinPred		0.11	T
GERP RS		3.5
gMVP		0.27

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-14994087;