Genetic Variant NM_001324445.2:c.499C>A (chr16-75612787-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001324445.2(ADAT1):c.499C>A(p.His167Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 1,613,702 control chromosomes in the GnomAD database, including 83,975 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.40 ( 15626 hom., cov: 32)

Exomes 𝑓: 0.27 ( 68349 hom. )

Consequence

ADAT1
NM_001324445.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0370

Publications

31 publications found

Variant links:

Genes affected

ADAT1 (HGNC:228): (adenosine deaminase tRNA specific 1) This gene is a member of the ADAR (adenosine deaminase acting on RNA) family. Using site-specific adenosine modification, proteins encoded by these genes participate in the pre-mRNA editing of nuclear transcripts. The protein encoded by this gene, tRNA-specific adenosine deaminase 1, is responsible for the deamination of adenosine 37 to inosine in eukaryotic tRNA. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jul 2010]

ADAT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.1302676E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAT1	NM_001324445.2 link	c.499C>A	p.His167Asn	missense_variant	Exon 6 of 10	ENST00000564657.2	NP_001311374.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAT1	ENST00000564657.2 link	c.499C>A	p.His167Asn	missense_variant	Exon 6 of 10	2	NM_001324445.2	ENSP00000457501.2

Frequencies

GnomAD3 genomes

AF:

0.400

AC:

60649

AN:

151720

Hom.:

15579

Cov.:

show subpopulations

Gnomad AFR

AF:

0.676

Gnomad AMI

AF:

0.252

Gnomad AMR

AF:

0.462

Gnomad ASJ

AF:

0.265

Gnomad EAS

AF:

0.814

Gnomad SAS

AF:

0.459

Gnomad FIN

AF:

0.217

Gnomad MID

AF:

0.282

Gnomad NFE

AF:

0.221

Gnomad OTH

AF:

0.368

GnomAD2 exomes

AF:

0.369

AC:

92107

AN:

249818

AF XY:

0.356

show subpopulations

Gnomad AFR exome

AF:

0.687

Gnomad AMR exome

AF:

0.526

Gnomad ASJ exome

AF:

0.244

Gnomad EAS exome

AF:

0.824

Gnomad FIN exome

AF:

0.215

Gnomad NFE exome

AF:

0.224

Gnomad OTH exome

AF:

0.315

GnomAD4 exome

AF:

0.273

AC:

398419

AN:

1461864

Hom.:

68349

Cov.:

AF XY:

0.275

AC XY:

199778

AN XY:

727230

show subpopulations

African (AFR)

AF:

0.687

AC:

22993

AN:

33480

American (AMR)

AF:

0.517

AC:

23098

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.248

AC:

6474

AN:

26134

East Asian (EAS)

AF:

0.812

AC:

32221

AN:

39700

South Asian (SAS)

AF:

0.434

AC:

37418

AN:

86258

European-Finnish (FIN)

AF:

0.224

AC:

11958

AN:

53412

Middle Eastern (MID)

AF:

0.286

AC:

1649

AN:

5766

European-Non Finnish (NFE)

AF:

0.219

AC:

243969

AN:

1112000

Other (OTH)

AF:

0.309

AC:

18639

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

17401

34802

52204

69605

87006

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8978

17956

26934

35912

44890

<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:

0.400

AC:

60764

AN:

151838

Hom.:

15626

Cov.:

AF XY:

0.403

AC XY:

29931

AN XY:

74192

show subpopulations

African (AFR)

AF:

0.676

AC:

28001

AN:

41396

American (AMR)

AF:

0.463

AC:

7056

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.265

AC:

920

AN:

3472

East Asian (EAS)

AF:

0.815

AC:

4197

AN:

5150

South Asian (SAS)

AF:

0.458

AC:

2202

AN:

4812

European-Finnish (FIN)

AF:

0.217

AC:

2281

AN:

10524

Middle Eastern (MID)

AF:

0.293

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.221

AC:

15014

AN:

67942

Other (OTH)

AF:

0.372

AC:

778

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1531

3062

4592

6123

7654

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

532

1064

1596

2128

2660

<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:

0.287

Hom.:

30464

Bravo

AF:

0.430

TwinsUK

AF:

0.217

AC:

805

ALSPAC

AF:

0.217

AC:

836

ESP6500AA

AF:

0.658

AC:

2893

ESP6500EA

AF:

0.214

AC:

1844

ExAC

AF:

0.369

AC:

44810

Asia WGS

AF:

0.643

AC:

2229

AN:

3478

EpiCase

AF:

0.225

EpiControl

AF:

0.228

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.35

(source)

DANN

Benign

0.69

DEOGEN2

Benign

0.039

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0089

LIST_S2

Benign

0.078

MetaRNN

Benign

0.0000011

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-1.0

PhyloP100

-0.037

PrimateAI

Benign

0.23

PROVEAN

Benign

1.1

REVEL

Benign

0.017

Sift

Benign

0.67

Sift4G

Benign

0.58

Vest4

0.037

ClinPred

0.00066

GERP RS

1.8

Varity_R

0.022

gMVP

0.25

Mutation Taster

=100/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over