dbSNP rs6136423: DTD1:c.44-128G>A (chr20-18593603-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_080820.6(DTD1):c.44-128G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 664,860 control chromosomes in the GnomAD database, including 7,222 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.14 ( 1715 hom., cov: 32)

Exomes 𝑓: 0.14 ( 5507 hom. )

Consequence

DTD1
NM_080820.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.32

Variant links:

Genes affected

DTD1 (HGNC:16219): (D-aminoacyl-tRNA deacylase 1) The protein encoded by this gene is similar in sequence to histidyl-tRNA synthetase, which hydrolyzes D-tyrosyl-tRNA(Tyr) into D-tyrosine and free tRNA(Tyr). The encoded protein binds the DNA unwinding element and plays a role in the initiation of DNA replication. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

DTD1 links:

ENSG00000284776 (HGNC:):

ENSG00000284776 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 (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DTD1	NM_080820.6 link	c.44-128G>A		intron_variant	Intron 1 of 5	ENST00000377452.4	NP_543010.3	Q8TEA8
DTD1	NM_001318043.2 link	c.44-128G>A		intron_variant	Intron 1 of 4		NP_001304972.1	Q8TEA8A0A2R8Y6X2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
DTD1	ENST00000377452.4 link	c.44-128G>A	intron_variant	Intron 1 of 5	1	NM_080820.6	ENSP00000366672.4	Q8TEA8
ENSG00000284776	ENST00000618693.4 link	c.119-128G>A	intron_variant	Intron 1 of 4	5		ENSP00000482916.1	A0A087WZV9
DTD1	ENST00000494921.2 link	c.44-128G>A	intron_variant	Intron 1 of 4	2		ENSP00000495845.1	A0A2R8Y6X2
DTD1	ENST00000647441.1 link	n.44-128G>A	intron_variant	Intron 1 of 6			ENSP00000493969.1	A0A2R8YCT7

Frequencies

GnomAD3 genomes

AF:

0.145

AC:

22044

AN:

152016

Hom.:

1717

Cov.:

show subpopulations

Gnomad AFR

AF:

0.127

Gnomad AMI

AF:

0.168

Gnomad AMR

AF:

0.197

Gnomad ASJ

AF:

0.167

Gnomad EAS

AF:

0.165

Gnomad SAS

AF:

0.0550

Gnomad FIN

AF:

0.166

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.144

Gnomad OTH

AF:

0.163

GnomAD4 exome

AF:

0.141

AC:

72206

AN:

512726

Hom.:

5507

AF XY:

0.136

AC XY:

37132

AN XY:

274034

show subpopulations

Gnomad4 AFR exome

AF:

0.127

AC:

1749

AN:

13788

Gnomad4 AMR exome

AF:

0.208

AC:

5636

AN:

27140

Gnomad4 ASJ exome

AF:

0.151

AC:

2477

AN:

16352

Gnomad4 EAS exome

AF:

0.151

AC:

4535

AN:

30086

Gnomad4 SAS exome

AF:

0.0621

AC:

3359

AN:

54054

Gnomad4 FIN exome

AF:

0.162

AC:

7259

AN:

44772

Gnomad4 NFE exome

AF:

0.145

AC:

42788

AN:

295202

Gnomad4 Remaining exome

AF:

0.140

AC:

3860

AN:

27644

Heterozygous variant carriers

2864

5728

8591

11455

14319

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

348

696

1044

1392

1740

<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:

0.145

AC:

22050

AN:

152134

Hom.:

1715

Cov.:

AF XY:

0.146

AC XY:

10826

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.127

AC:

0.127137

AN:

0.127137

Gnomad4 AMR

AF:

0.197

AC:

0.197303

AN:

0.197303

Gnomad4 ASJ

AF:

0.167

AC:

0.166859

AN:

0.166859

Gnomad4 EAS

AF:

0.165

AC:

0.165251

AN:

0.165251

Gnomad4 SAS

AF:

0.0555

AC:

0.0554632

AN:

0.0554632

Gnomad4 FIN

AF:

0.166

AC:

0.165563

AN:

0.165563

Gnomad4 NFE

AF:

0.144

AC:

0.143569

AN:

0.143569

Gnomad4 OTH

AF:

0.161

AC:

0.161306

AN:

0.161306

Heterozygous variant carriers

979

1959

2938

3918

4897

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

232

464

696

928

1160

<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:

0.150

Hom.:

238

Bravo

AF:

0.150

Asia WGS

AF:

0.105

AC:

365

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.087

DANN

Benign

0.64

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over