chr16-75612787-G-T

Position:

• chr16-75612787-G-T

Variant summary

Our verdict is Benign. Variant got -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. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• 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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
ADAT1	NM_001324445.2	c.499C>A	p.His167Asn	missense_variant	6/10	ENST00000564657.2	NP_001311374.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAT1	ENST00000564657.2	c.499C>A	p.His167Asn	missense_variant	6/10	2	NM_001324445.2	ENSP00000457501.2

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

GnomAD3 exomes AF: 0.369 AC: 92107 AN: 249818 Hom.: 22050 AF XY: 0.356 AC XY: 48139 AN XY: 135212

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 SAS exome AF: 0.440

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

Gnomad4 AFR exome AF: 0.687

Gnomad4 AMR exome AF: 0.517

Gnomad4 ASJ exome AF: 0.248

Gnomad4 EAS exome AF: 0.812

Gnomad4 SAS exome AF: 0.434

Gnomad4 FIN exome AF: 0.224

Gnomad4 NFE exome AF: 0.219

Gnomad4 OTH exome AF: 0.309

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

Gnomad4 AFR AF: 0.676

Gnomad4 AMR AF: 0.463

Gnomad4 ASJ AF: 0.265

Gnomad4 EAS AF: 0.815

Gnomad4 SAS AF: 0.458

Gnomad4 FIN AF: 0.217

Gnomad4 NFE AF: 0.221

Gnomad4 OTH AF: 0.372

Alfa AF: 0.274 Hom.: 14461

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	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
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

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

LitVar

Other links and lift over

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