NM_001324445.2:c.499C>A

Variant names:

• chr16-75612787-G-T
• rs3743598
• NM_001324445.2:c.499C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0370
• Publications: 31 publications found

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]

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001324445.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAT1	NM_001324445.2	MANE Select	c.499C>A	p.His167Asn	missense	Exon 6 of 10	NP_001311374.1
	ADAT1	NM_012091.5		c.499C>A	p.His167Asn	missense	Exon 7 of 11	NP_036223.2
	ADAT1	NM_001324448.2		c.499C>A	p.His167Asn	missense	Exon 7 of 9	NP_001311377.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAT1	ENST00000564657.2	TSL:2 MANE Select	c.499C>A	p.His167Asn	missense	Exon 6 of 10	ENSP00000457501.2
	ADAT1	ENST00000307921.7	TSL:1	c.499C>A	p.His167Asn	missense	Exon 7 of 11	ENSP00000310015.3
	ADAT1	ENST00000566445.5	TSL:5	n.*245C>A		non_coding_transcript_exon	Exon 6 of 10	ENSP00000456768.1

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60649 AN: 151720 Hom.: 15579 Cov.: 32

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

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.: 37 AF XY: 0.275 AC XY: 199778 AN XY: 727230

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

GnomAD4 genome AF: 0.400 AC: 60764 AN: 151838 Hom.: 15626 Cov.: 32 AF XY: 0.403 AC XY: 29931 AN XY: 74192

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: 86 AN: 294

European-Non Finnish (NFE) AF: 0.221 AC: 15014 AN: 67942

Other (OTH) AF: 0.372 AC: 778 AN: 2094

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.35
DANN	Benign	0.69
DEOGEN2	Benign	0.039	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0089	N
LIST_S2	Benign	0.078	T
MetaRNN	Benign	0.0000011	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-1.0	N
PhyloP100		-0.037
PrimateAI	Benign	0.23	T
PROVEAN	Benign	1.1	N
REVEL	Benign	0.017
Sift	Benign	0.67	T
Sift4G	Benign	0.58	T
Polyphen		0.0	B
Vest4		0.037
MPC		0.0077
ClinPred		0.00066	T
GERP RS		1.8
Varity_R		0.022
gMVP		0.25
Mutation Taster		=100/0	polymorphism (auto)

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: rs3743598; hg19: chr16-75646685; COSMIC: COSV57185223; COSMIC: COSV57185223;