Variant 15-88527755-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001144074.3(DET1):c.1115C>T(p.Thr372Met) variant causes a missense change. The variant allele was found at a frequency of 0.000293 in 1,611,626 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00029 ( 0 hom. )

Consequence

DET1
NM_001144074.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.13

Variant links:

Genes affected

DET1 (HGNC:25477): (DET1 partner of COP1 E3 ubiquitin ligase) Enables ubiquitin ligase-substrate adaptor activity and ubiquitin protein ligase binding activity. Involved in positive regulation of proteasomal ubiquitin-dependent protein catabolic process; protein ubiquitination; and protein-containing complex assembly. Part of Cul4A-RING E3 ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

DET1 links:

ENSG00000173867 (HGNC:):

ENSG00000173867 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18468374).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DET1	NM_001144074.3 linkuse as main transcript	c.1115C>T	p.Thr372Met	missense_variant	3/5	ENST00000268148.13	NP_001137546.1	Q7L5Y6-1A0A024RC56

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DET1	ENST00000268148.13 linkuse as main transcript	c.1115C>T	p.Thr372Met	missense_variant	3/5	1	NM_001144074.3	ENSP00000268148.8		Q7L5Y6-1
ENSG00000173867	ENST00000649547.1 linkuse as main transcript	c.1115C>T	p.Thr372Met	missense_variant	4/10			ENSP00000497509.1

Frequencies

GnomAD3 genomes

AF:

0.000283

AC:

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000368

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000300

AC:

AN:

246260

Hom.:

AF XY:

0.000329

AC XY:

AN XY:

133598

show subpopulations

Gnomad AFR exome

AF:

0.000130

Gnomad AMR exome

AF:

0.000324

Gnomad ASJ exome

AF:

0.000304

Gnomad EAS exome

AF:

0.000112

Gnomad SAS exome

AF:

0.000133

Gnomad FIN exome

AF:

0.000842

Gnomad NFE exome

AF:

0.000296

Gnomad OTH exome

AF:

0.000167

GnomAD4 exome

AF:

0.000294

AC:

429

AN:

1459398

Hom.:

Cov.:

AF XY:

0.000255

AC XY:

185

AN XY:

725832

show subpopulations

Gnomad4 AFR exome

AF:

0.000330

Gnomad4 AMR exome

AF:

0.000316

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.000140

Gnomad4 FIN exome

AF:

0.000750

Gnomad4 NFE exome

AF:

0.000286

Gnomad4 OTH exome

AF:

0.000365

GnomAD4 genome

AF:

0.000282

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.000368

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000236

Hom.:

Bravo

AF:

0.000249

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000483

AC:

ExAC

AF:

0.000273

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000219

EpiControl

AF:

0.000298

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

Oct 12, 2021

The c.1148C>T (p.T383M) alteration is located in exon 4 (coding exon 3) of the DET1 gene. This alteration results from a C to T substitution at nucleotide position 1148, causing the threonine (T) at amino acid position 383 to be replaced by a methionine (M). 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

Benign

0.25

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.20

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.62

.;.;.;D

Eigen

Uncertain

0.63

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.97

.;D;.;D

M_CAP

Benign

0.011

MetaRNN

Benign

0.18

T;T;T;T

MetaSVM

Benign

-0.56

MutationAssessor

Benign

1.8

.;.;.;L

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-3.1

.;D;D;D

REVEL

Uncertain

0.44

Sift

Uncertain

0.0050

.;D;D;D

Sift4G

Uncertain

0.043

.;D;D;D

Polyphen

0.91

.;.;.;P

Vest4

0.58, 0.57, 0.58

MVP

0.11

MPC

0.65

ClinPred

0.12

GERP RS

5.9

Varity_R

0.17

gMVP

0.58

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