Variant 1-212043027-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_016448.4(DTL):c.87G>A(p.Leu29Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00382 in 1,612,674 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0028 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0039 ( 15 hom. )

Consequence

DTL
NM_016448.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.221

Variant links:

Genes affected

DTL (HGNC:30288): (denticleless E3 ubiquitin protein ligase homolog) Contributes to ubiquitin-protein transferase activity. Involved in several processes, including protein ubiquitination; regulation of G2/M transition of mitotic cell cycle; and translesion synthesis. Located in centrosome; cytosol; and nuclear lumen. Part of Cul4A-RING E3 ubiquitin ligase complex and Cul4B-RING E3 ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

DTL links:

DTL (HGNC:):

DTL links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 1-212043027-G-A is Benign according to our data. Variant chr1-212043027-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2639883.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.221 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DTL	NM_016448.4 linkuse as main transcript	c.87G>A	p.Leu29Leu	synonymous_variant	2/15	ENST00000366991.5	NP_057532.4	Q9NZJ0-1
DTL	XM_011509614.2 linkuse as main transcript	c.-100G>A		5_prime_UTR_variant	2/15		XP_011507916.1
DTL	NM_001286230.2 linkuse as main transcript	c.53-1633G>A		intron_variant			NP_001273159.2	B4E0E6
DTL	NM_001286229.2 linkuse as main transcript	c.-531-1633G>A		intron_variant			NP_001273158.2	Q9NZJ0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DTL	ENST00000366991.5 linkuse as main transcript	c.87G>A	p.Leu29Leu	synonymous_variant	2/15	1	NM_016448.4	ENSP00000355958.4	Q9NZJ0-1
DTL	ENST00000542077.5 linkuse as main transcript	c.53-1633G>A		intron_variant		2		ENSP00000443870.1	F5GZ90
DTL	ENST00000475419.5 linkuse as main transcript	n.98-1633G>A		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00281

AC:

428

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000965

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.00478

Gnomad ASJ

AF:

0.00432

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00407

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00296

AC:

741

AN:

250252

Hom.:

AF XY:

0.00308

AC XY:

417

AN XY:

135300

show subpopulations

Gnomad AFR exome

AF:

0.000741

Gnomad AMR exome

AF:

0.00401

Gnomad ASJ exome

AF:

0.00388

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000987

Gnomad FIN exome

AF:

0.000370

Gnomad NFE exome

AF:

0.00459

Gnomad OTH exome

AF:

0.00361

GnomAD4 exome

AF:

0.00392

AC:

5731

AN:

1460374

Hom.:

Cov.:

AF XY:

0.00382

AC XY:

2775

AN XY:

726510

show subpopulations

Gnomad4 AFR exome

AF:

0.000628

Gnomad4 AMR exome

AF:

0.00420

Gnomad4 ASJ exome

AF:

0.00349

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.000209

Gnomad4 FIN exome

AF:

0.000562

Gnomad4 NFE exome

AF:

0.00462

Gnomad4 OTH exome

AF:

0.00365

GnomAD4 genome

AF:

0.00281

AC:

428

AN:

152300

Hom.:

Cov.:

AF XY:

0.00240

AC XY:

179

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000962

Gnomad4 AMR

AF:

0.00477

Gnomad4 ASJ

AF:

0.00432

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.00407

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00390

Hom.:

Bravo

AF:

0.00331

Asia WGS

AF:

0.000289

AC:

AN:

3476

EpiCase

AF:

0.00492

EpiControl

AF:

0.00505

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

DTL: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

2.3

DANN

Benign

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over