12-14841153-C-T

Variant names:

• chr12-14841153-C-T
• rs1341098396
• NM_021071.4:c.145G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021071.4(ART4):​c.145G>A​(p.Val49Ile) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000319 in 1,567,240 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: ART4 NM_021071.4 missense, splice_region
• Scores: Splicing: ADA: 0.05289
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.39
• 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]

ENSG00000256339 (HGNC:):

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

ACMG classification

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=0.09577751).

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>A	p.Val49Ile	missense splice_region	Exon 2 of 3	NP_066549.2	Q93070
	ART4	NM_001354646.2		c.145G>A	p.Val49Ile	missense splice_region	Exon 2 of 2	NP_001341575.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ART4	ENST00000228936.6	TSL:1 MANE Select	c.145G>A	p.Val49Ile	missense splice_region	Exon 2 of 3	ENSP00000228936.4	Q93070
	ART4	ENST00000420600.2	TSL:1	c.94G>A	p.Val32Ile	missense splice_region	Exon 2 of 2	ENSP00000405689.1	H7C2G2
	ART4	ENST00000430129.6	TSL:1	c.94G>A	p.Val32Ile	missense splice_region	Exon 2 of 3	ENSP00000412735.2	Q3KZ30

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152072 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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: 0.00000283 AC: 4 AN: 1415168 Hom.: 0 Cov.: 32 AF XY: 0.00000142 AC XY: 1 AN XY: 701890

African (AFR) AF: 0.00 AC: 0 AN: 30864

American (AMR) AF: 0.00 AC: 0 AN: 32000

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23178

East Asian (EAS) AF: 0.00 AC: 0 AN: 39342

South Asian (SAS) AF: 0.00 AC: 0 AN: 78864

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51936

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5534

European-Non Finnish (NFE) AF: 0.00000365 AC: 4 AN: 1095240

Other (OTH) AF: 0.00 AC: 0 AN: 58210

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152072 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74276

African (AFR) AF: 0.00 AC: 0 AN: 41396

American (AMR) AF: 0.00 AC: 0 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	9.0
DANN	Benign	0.93
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.096	T
MetaSVM	Benign	-0.97	T
PhyloP100		1.4
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.19	N
REVEL	Benign	0.039
Sift	Benign	0.28	T
Sift4G	Benign	0.26	T
Vest4		0.035
MutPred		0.25		Loss of sheet (P = 0.1398)
MVP		0.16
MPC		0.010
ClinPred		0.074	T
GERP RS		3.5
gMVP		0.094
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.053
dbscSNV1_RF	Benign	0.24
SpliceAI score (max)		0.010		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: rs1341098396; hg19: chr12-14994087;