Genetic Variant DTWD1:n.-24G>A (chr15-49625144-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 ENST00000557968.5(DTWD1):n.-24G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 1,602,110 control chromosomes in the GnomAD database, including 50,386 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 0.19 ( 3510 hom., cov: 32)

Exomes 𝑓: 0.24 ( 46876 hom. )

Consequence

DTWD1
ENST00000557968.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.218

Publications

10 publications found

Variant links:

Genes affected

DTWD1 (HGNC:30926): (DTW domain containing 1) Enables tRNA-uridine aminocarboxypropyltransferase activity. Involved in tRNA modification. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

DTWD1 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=-0.82).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000557968.5. 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
	DTWD1	NM_001144955.2	MANE Select	c.-24G>A		5_prime_UTR	Exon 2 of 5	NP_001138427.1
	DTWD1	NM_020234.6		c.-24G>A		5_prime_UTR	Exon 3 of 6	NP_064619.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
DTWD1	ENST00000557968.5	TSL:1	n.-24G>A	non_coding_transcript_exon	Exon 2 of 4	ENSP00000452628.1
DTWD1	ENST00000557988.5	TSL:1	n.-24G>A	non_coding_transcript_exon	Exon 2 of 6	ENSP00000453686.1
DTWD1	ENST00000403028.8	TSL:1 MANE Select	c.-24G>A	5_prime_UTR	Exon 2 of 5	ENSP00000385399.3

Frequencies

GnomAD3 genomes

AF:

0.194

AC:

29420

AN:

151758

Hom.:

3513

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0668

Gnomad AMI

AF:

0.223

Gnomad AMR

AF:

0.180

Gnomad ASJ

AF:

0.260

Gnomad EAS

AF:

0.00483

Gnomad SAS

AF:

0.176

Gnomad FIN

AF:

0.324

Gnomad MID

AF:

0.223

Gnomad NFE

AF:

0.266

Gnomad OTH

AF:

0.210

GnomAD2 exomes

AF:

0.209

AC:

51244

AN:

245284

AF XY:

0.215

show subpopulations

Gnomad AFR exome

AF:

0.0592

Gnomad AMR exome

AF:

0.124

Gnomad ASJ exome

AF:

0.260

Gnomad EAS exome

AF:

0.00120

Gnomad FIN exome

AF:

0.328

Gnomad NFE exome

AF:

0.265

Gnomad OTH exome

AF:

0.249

GnomAD4 exome

AF:

0.245

AC:

354663

AN:

1450234

Hom.:

46876

Cov.:

AF XY:

0.245

AC XY:

176469

AN XY:

721164

show subpopulations

African (AFR)

AF:

0.0585

AC:

1936

AN:

33122

American (AMR)

AF:

0.130

AC:

5728

AN:

44010

Ashkenazi Jewish (ASJ)

AF:

0.263

AC:

6808

AN:

25860

East Asian (EAS)

AF:

0.000936

AC:

AN:

39540

South Asian (SAS)

AF:

0.198

AC:

16877

AN:

85398

European-Finnish (FIN)

AF:

0.324

AC:

17155

AN:

52894

Middle Eastern (MID)

AF:

0.291

AC:

1662

AN:

5718

European-Non Finnish (NFE)

AF:

0.263

AC:

290350

AN:

1103756

Other (OTH)

AF:

0.235

AC:

14110

AN:

59936

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

11097

22193

33290

44386

55483

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9414

18828

28242

37656

47070

<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:

0.194

AC:

29410

AN:

151876

Hom.:

3510

Cov.:

AF XY:

0.195

AC XY:

14483

AN XY:

74212

show subpopulations

African (AFR)

AF:

0.0667

AC:

2766

AN:

41440

American (AMR)

AF:

0.179

AC:

2736

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.260

AC:

902

AN:

3470

East Asian (EAS)

AF:

0.00503

AC:

AN:

5168

South Asian (SAS)

AF:

0.175

AC:

840

AN:

4812

European-Finnish (FIN)

AF:

0.324

AC:

3398

AN:

10488

Middle Eastern (MID)

AF:

0.212

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.266

AC:

18039

AN:

67930

Other (OTH)

AF:

0.208

AC:

438

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1166

2332

3499

4665

5831

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

314

628

942

1256

1570

<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:

0.243

Hom.:

2596

Bravo

AF:

0.177

Asia WGS

AF:

0.0770

AC:

267

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

(source)

DANN

Benign

0.86

PhyloP100

0.22

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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