dbSNP rs1006771: DDTL:c.*411G>T (chr22-23971817-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_001084393.2(DDTL):c.*411G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.658 in 600,156 control chromosomes in the GnomAD database, including 130,583 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 0.67 ( 33832 hom., cov: 32)

Exomes 𝑓: 0.65 ( 96751 hom. )

Consequence

DDTL
NM_001084393.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.53

Publications

44 publications found

Variant links:

Genes affected

DDTL (HGNC:33446): (D-dopachrome tautomerase like) Predicted to enable lyase activity. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

DDTL links:

DDT (HGNC:2732): (D-dopachrome tautomerase) D-dopachrome tautomerase converts D-dopachrome into 5,6-dihydroxyindole. The DDT gene is related to the migration inhibitory factor (MIF) in terms of sequence, enzyme activity, and gene structure. DDT and MIF are closely linked on chromosome 22. [provided by RefSeq, Jul 2008]

DDT links:

ENSG00000290199 (HGNC:):

ENSG00000290199 links:

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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=-0.84).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.714 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
DDTL	NM_001084393.2 link	c.*411G>T	3_prime_UTR_variant	Exon 3 of 3	ENST00000215770.6	NP_001077862.1	A6NHG4A0A0F7RPW6
DDT	NM_001084392.3 link	c.285-194C>A	intron_variant	Intron 2 of 2	ENST00000398344.9	NP_001077861.1	P30046-1Q53Y51
DDT	NM_001355.4 link	c.285-194C>A	intron_variant	Intron 3 of 3		NP_001346.1	P30046-1Q53Y51
DDT	NM_001397485.1 link	c.285-194C>A	intron_variant	Intron 3 of 3		NP_001384414.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDTL	ENST00000215770.6 link	c.*411G>T		3_prime_UTR_variant	Exon 3 of 3	2	NM_001084393.2	ENSP00000215770.5		A6NHG4
DDT	ENST00000398344.9 link	c.285-194C>A		intron_variant	Intron 2 of 2	1	NM_001084392.3	ENSP00000381386.4		P30046-1

Frequencies

GnomAD3 genomes

AF:

0.668

AC:

101132

AN:

151378

Hom.:

33811

Cov.:

show subpopulations

Gnomad AFR

AF:

0.699

Gnomad AMI

AF:

0.811

Gnomad AMR

AF:

0.646

Gnomad ASJ

AF:

0.680

Gnomad EAS

AF:

0.550

Gnomad SAS

AF:

0.732

Gnomad FIN

AF:

0.695

Gnomad MID

AF:

0.687

Gnomad NFE

AF:

0.651

Gnomad OTH

AF:

0.658

GnomAD4 exome

AF:

0.654

AC:

293462

AN:

448662

Hom.:

96751

Cov.:

AF XY:

0.657

AC XY:

155192

AN XY:

236090

show subpopulations

African (AFR)

AF:

0.701

AC:

8705

AN:

12414

American (AMR)

AF:

0.637

AC:

11338

AN:

17802

Ashkenazi Jewish (ASJ)

AF:

0.674

AC:

9120

AN:

13538

East Asian (EAS)

AF:

0.528

AC:

15670

AN:

29658

South Asian (SAS)

AF:

0.718

AC:

31429

AN:

43760

European-Finnish (FIN)

AF:

0.702

AC:

20632

AN:

29388

Middle Eastern (MID)

AF:

0.647

AC:

1274

AN:

1970

European-Non Finnish (NFE)

AF:

0.650

AC:

178472

AN:

274420

Other (OTH)

AF:

0.654

AC:

16822

AN:

25712

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

4780

9560

14339

19119

23899

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.668

AC:

101203

AN:

151494

Hom.:

33832

Cov.:

AF XY:

0.673

AC XY:

49777

AN XY:

73972

show subpopulations

African (AFR)

AF:

0.699

AC:

29001

AN:

41486

American (AMR)

AF:

0.646

AC:

9876

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.680

AC:

2360

AN:

3470

East Asian (EAS)

AF:

0.550

AC:

2621

AN:

4766

South Asian (SAS)

AF:

0.734

AC:

3535

AN:

4816

European-Finnish (FIN)

AF:

0.695

AC:

7244

AN:

10426

Middle Eastern (MID)

AF:

0.687

AC:

202

AN:

294

European-Non Finnish (NFE)

AF:

0.651

AC:

44246

AN:

67942

Other (OTH)

AF:

0.655

AC:

1380

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

1744

3489

5233

6978

8722

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.659

Hom.:

49421

Bravo

AF:

0.661

Asia WGS

AF:

0.661

AC:

2295

AN:

3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

2.3

(source)

DANN

Benign

0.51

PhyloP100

1.5

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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rs1006771

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