Variant 11-59182297-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_015177.2(DTX4):c.770T>G(p.Val257Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000625 in 1,612,324 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0033 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00035 ( 4 hom. )

Consequence

DTX4
NM_015177.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.822

Variant links:

Genes affected

DTX4 (HGNC:29151): (deltex E3 ubiquitin ligase 4) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in Notch signaling pathway and protein ubiquitination. Predicted to be located in cytosol. Predicted to be active in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

DTX4 links:

LOC124902675 (HGNC:):

LOC124902675 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003544569).

BP6

Variant 11-59182297-T-G is Benign according to our data. Variant chr11-59182297-T-G is described in ClinVar as [Benign]. Clinvar id is 716947.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 500 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
DTX4	NM_015177.2 linkuse as main transcript	c.770T>G	p.Val257Gly	missense_variant	2/9	ENST00000227451.4	NP_055992.1
LOC124902675	XR_007062682.1 linkuse as main transcript	n.2649-2478A>C		intron_variant, non_coding_transcript_variant
DTX4	NM_001300727.2 linkuse as main transcript	c.452T>G	p.Val151Gly	missense_variant	2/9		NP_001287656.1
LOC124902675	XR_007062681.1 linkuse as main transcript	n.2649-2478A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DTX4	ENST00000227451.4 linkuse as main transcript	c.770T>G	p.Val257Gly	missense_variant	2/9	1	NM_015177.2	ENSP00000227451	P1	Q9Y2E6-1
DTX4	ENST00000532982.5 linkuse as main transcript	c.452T>G	p.Val151Gly	missense_variant	2/9	1		ENSP00000434055		Q9Y2E6-2

Frequencies

GnomAD3 genomes

AF:

0.00329

AC:

500

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0114

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000981

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.000877

AC:

216

AN:

246418

Hom.:

AF XY:

0.000686

AC XY:

AN XY:

134040

show subpopulations

Gnomad AFR exome

AF:

0.0123

Gnomad AMR exome

AF:

0.000581

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000712

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000347

AC:

507

AN:

1460084

Hom.:

Cov.:

AF XY:

0.000300

AC XY:

218

AN XY:

726444

show subpopulations

Gnomad4 AFR exome

AF:

0.0113

Gnomad4 AMR exome

AF:

0.000514

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000387

Gnomad4 OTH exome

AF:

0.000845

GnomAD4 genome

AF:

0.00328

AC:

500

AN:

152240

Hom.:

Cov.:

AF XY:

0.00322

AC XY:

240

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.0114

Gnomad4 AMR

AF:

0.000980

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.000540

Hom.:

Bravo

AF:

0.00364

ESP6500AA

AF:

0.00736

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000884

AC:

107

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 26, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.43

DANN

Benign

0.62

DEOGEN2

Benign

0.017

.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.093

LIST_S2

Benign

0.32

T;T

MetaRNN

Benign

0.0035

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.0

.;N

MutationTaster

Benign

0.86

N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

0.34

N;N

REVEL

Benign

0.041

Sift

Benign

0.53

T;T

Sift4G

Benign

0.55

T;T

Polyphen

0.0

.;B

Vest4

0.11

MVP

0.18

MPC

0.41

ClinPred

0.00055

GERP RS

-1.6

Varity_R

0.041

gMVP

0.29

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over