Genetic Variant ADI1:p.Glu152Lys (chr2-3499049-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_018269.4(ADI1):c.454G>A(p.Glu152Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000968 in 1,614,138 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E152Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00075 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00099 ( 0 hom. )

Consequence

ADI1
NM_018269.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.44

Publications

5 publications found

Variant links:

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]

ADI1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.103964746).

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>A	p.Glu152Lys	missense	Exon 4 of 4	NP_060739.2	Q9BV57-1
	ADI1	NM_001306077.2		c.436G>A	p.Glu146Lys	missense	Exon 4 of 4	NP_001293006.1	Q9BV57-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADI1	ENST00000327435.11	TSL:1 MANE Select	c.454G>A	p.Glu152Lys	missense	Exon 4 of 4	ENSP00000333666.3	Q9BV57-1
ADI1	ENST00000879405.1		c.592G>A	p.Glu198Lys	missense	Exon 4 of 4	ENSP00000549464.1
ADI1	ENST00000879404.1		c.553G>A	p.Glu185Lys	missense	Exon 5 of 5	ENSP00000549463.1

Frequencies

GnomAD3 genomes

AF:

0.000755

AC:

115

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00118

Gnomad OTH

AF:

0.000955

GnomAD2 exomes

AF:

0.000465

AC:

117

AN:

251430

AF XY:

0.000500

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.000844

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000990

AC:

1447

AN:

1461770

Hom.:

Cov.:

AF XY:

0.000906

AC XY:

659

AN XY:

727164

show subpopulations

African (AFR)

AF:

0.000269

AC:

AN:

33478

American (AMR)

AF:

0.000291

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.000262

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00123

AC:

1365

AN:

1111904

Other (OTH)

AF:

0.000762

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

160

240

320

400

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

112

168

224

280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000755

AC:

115

AN:

152368

Hom.:

Cov.:

AF XY:

0.000738

AC XY:

AN XY:

74516

show subpopulations

African (AFR)

AF:

0.000313

AC:

AN:

41580

American (AMR)

AF:

0.00111

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.000282

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00118

AC:

AN:

68040

Other (OTH)

AF:

0.000945

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000851

Hom.:

Bravo

AF:

0.000642

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00311

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000379

AC:

EpiCase

AF:

0.000709

EpiControl

AF:

0.00113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.19

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.52

Eigen

Benign

0.11

Eigen_PC

Benign

0.045

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.018

MetaRNN

Benign

0.10

MetaSVM

Uncertain

-0.28

MutationAssessor

Pathogenic

3.6

PhyloP100

4.4

PrimateAI

Benign

0.40

PROVEAN

Uncertain

-3.2

REVEL

Uncertain

0.42

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.010

Polyphen

0.044

Vest4

0.32

MVP

0.35

MPC

0.33

ClinPred

0.57

GERP RS

2.7

Varity_R

0.48

gMVP

0.67

Mutation Taster

=41/59

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over