chr2-3499049-C-G

Variant names:

• chr2-3499049-C-G
• rs143494796
• NM_018269.4:c.454G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018269.4(ADI1):​c.454G>C​(p.Glu152Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ADI1 NM_018269.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.44
• Publications: 0 publications found

Genes affected

ADI1 (HGNC:30576): (acireductone dioxygenase 1) This gene encodes an enzyme that belongs to the aci-reductone dioxygenase family of metal-binding enzymes, which are involved in methionine salvage. This enzyme may regulate mRNA processing in the nucleus, and may carry out different functions depending on its localization. Related pseudogenes have been defined on chromosomes 8 and 20. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2015]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27552786).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018269.4. 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
	ADI1	NM_018269.4	MANE Select	c.454G>C	p.Glu152Gln	missense	Exon 4 of 4	NP_060739.2	Q9BV57-1
	ADI1	NM_001306077.2		c.436G>C	p.Glu146Gln	missense	Exon 4 of 4	NP_001293006.1	Q9BV57-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADI1	ENST00000327435.11	TSL:1 MANE Select	c.454G>C	p.Glu152Gln	missense	Exon 4 of 4	ENSP00000333666.3	Q9BV57-1
	ADI1	ENST00000879405.1		c.592G>C	p.Glu198Gln	missense	Exon 4 of 4	ENSP00000549464.1
	ADI1	ENST00000879404.1		c.553G>C	p.Glu185Gln	missense	Exon 5 of 5	ENSP00000549463.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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	0.20
BayesDel_addAF	Benign	-0.068	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.41	T
Eigen	Benign	0.086
Eigen_PC	Benign	0.029
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.39	T
MutationAssessor	Pathogenic	3.5	M
PhyloP100		4.4
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.18
Sift	Uncertain	0.023	D
Sift4G	Uncertain	0.041	D
Polyphen		0.011	B
Vest4		0.12
MutPred		0.52		Gain of MoRF binding (P = 0.0343)
MVP		0.42
MPC		0.17
ClinPred		0.97	D
GERP RS		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.34
gMVP		0.58
Mutation Taster		=44/56	disease causing

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: rs143494796; hg19: chr2-3502820;