Variant 1-212065019-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_016448.4(DTL):c.629C>T(p.Ala210Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000199 in 1,611,758 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 2 hom., cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

DTL
NM_016448.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.07

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.3094132).

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.629C>T	p.Ala210Val	missense_variant	7/15	ENST00000366991.5	NP_057532.4	Q9NZJ0-1
DTL	NM_001286230.2 linkuse as main transcript	c.503C>T	p.Ala168Val	missense_variant	6/14		NP_001273159.2	B4E0E6
DTL	XM_011509614.2 linkuse as main transcript	c.443C>T	p.Ala148Val	missense_variant	7/15		XP_011507916.1
DTL	NM_001286229.2 linkuse as main transcript	c.-81C>T		5_prime_UTR_variant	6/13		NP_001273158.2	Q9NZJ0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DTL	ENST00000366991.5 linkuse as main transcript	c.629C>T	p.Ala210Val	missense_variant	7/15	1	NM_016448.4	ENSP00000355958.4	Q9NZJ0-1
DTL	ENST00000542077.5 linkuse as main transcript	c.503C>T	p.Ala168Val	missense_variant	6/14	2		ENSP00000443870.1	F5GZ90
DTL	ENST00000475419.5 linkuse as main transcript	n.548C>T		non_coding_transcript_exon_variant	6/13	2

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000239

AC:

AN:

251116

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135720

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000130

AC:

AN:

1459450

Hom.:

Cov.:

AF XY:

0.00000826

AC XY:

AN XY:

726198

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152308

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000850

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.000223

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 19, 2023

The c.629C>T (p.A210V) alteration is located in exon 7 (coding exon 7) of the DTL gene. This alteration results from a C to T substitution at nucleotide position 629, causing the alanine (A) at amino acid position 210 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.44

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

0.0

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.11

.;T

Eigen

Pathogenic

0.75

Eigen_PC

Pathogenic

0.73

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

D;D

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.31

T;T

MetaSVM

Uncertain

-0.078

MutationAssessor

Uncertain

2.4

.;M

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.92

N;N

REVEL

Uncertain

0.32

Sift

Benign

0.075

T;T

Sift4G

Benign

0.061

T;T

Polyphen

1.0

D;D

Vest4

0.72

MVP

0.84

MPC

0.59

ClinPred

0.71

GERP RS

5.4

Varity_R

0.20

gMVP

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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