chr12-14841132-C-T

Variant names:

• chr12-14841132-C-T
• rs775874295
• NM_021071.4:c.166G>A

Variant summary

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

The NM_021071.4(ART4):​c.166G>A​(p.Asp56Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000108 in 1,571,064 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: ART4 NM_021071.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.71
• Publications: 0 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 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ART4	NM_021071.4	MANE Select	c.166G>A	p.Asp56Asn	missense	Exon 2 of 3	NP_066549.2	Q93070
	ART4	NM_001354646.2		c.166G>A	p.Asp56Asn	missense	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.166G>A	p.Asp56Asn	missense	Exon 2 of 3	ENSP00000228936.4	Q93070
	ART4	ENST00000420600.2	TSL:1	c.115G>A	p.Asp39Asn	missense	Exon 2 of 2	ENSP00000405689.1	H7C2G2
	ART4	ENST00000430129.6	TSL:1	c.115G>A	p.Asp39Asn	missense	Exon 2 of 3	ENSP00000412735.2	Q3KZ30

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152102 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

GnomAD2 exomes AF: 0.0000138 AC: 3 AN: 216826 AF XY: 0.00000848

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000414

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000963

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000113 AC: 16 AN: 1418962 Hom.: 0 Cov.: 32 AF XY: 0.0000128 AC XY: 9 AN XY: 703086

African (AFR) AF: 0.0000322 AC: 1 AN: 31042

American (AMR) AF: 0.0000300 AC: 1 AN: 33324

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23802

East Asian (EAS) AF: 0.00 AC: 0 AN: 39288

South Asian (SAS) AF: 0.0000125 AC: 1 AN: 79942

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52478

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5576

European-Non Finnish (NFE) AF: 0.0000110 AC: 12 AN: 1095166

Other (OTH) AF: 0.0000171 AC: 1 AN: 58344

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152102 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74292

African (AFR) AF: 0.00 AC: 0 AN: 41412

American (AMR) AF: 0.00 AC: 0 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.0000595

ClinVar

ClinVar submissions as Germline

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	0.10
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.34
Eigen_PC	Benign	0.19
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.56	D
MetaSVM	Benign	-0.97	T
PhyloP100		1.7
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.21
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.013	D
Vest4		0.22
MutPred		0.64		Loss of ubiquitination at K52 (P = 0.1264)
MVP		0.50
MPC		0.016
ClinPred		0.98	D
GERP RS		0.52
gMVP		0.58
Mutation Taster		=94/6	polymorphism

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: rs775874295; hg19: chr12-14994066; COSMIC: COSV99966843;