2-3499049-C-G

Position:

• chr2-3499049-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 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. 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

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADI1	NM_018269.4	c.454G>C	p.Glu152Gln	missense_variant	4/4	ENST00000327435.11	NP_060739.2
ADI1	NM_001306077.2	c.436G>C	p.Glu146Gln	missense_variant	4/4		NP_001293006.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADI1	ENST00000327435.11	c.454G>C	p.Glu152Gln	missense_variant	4/4	1	NM_018269.4	ENSP00000333666	P1
ADI1	ENST00000382093.5	c.436G>C	p.Glu146Gln	missense_variant	4/4	2		ENSP00000371525
ADI1	ENST00000415131.1	c.268G>C	p.Glu90Gln	missense_variant	2/2	3		ENSP00000410178

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 12, 2021

The c.454G>C (p.E152Q) alteration is located in exon 4 (coding exon 4) of the ADI1 gene. This alteration results from a G to C substitution at nucleotide position 454, causing the glutamic acid (E) at amino acid position 152 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;D
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.28	T;T
MetaSVM	Benign	-0.39	T
MutationAssessor	Pathogenic	3.5	M;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-2.4	N;N
REVEL	Benign	0.18
Sift	Uncertain	0.023	D;D
Sift4G	Uncertain	0.041	D;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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-3502820;