Variant 15-88527720-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001144074.3(DET1):c.1150G>C(p.Asp384His) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,613,750 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 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

DET1
NM_001144074.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.79

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.33750477).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DET1	NM_001144074.3 linkuse as main transcript	c.1150G>C	p.Asp384His	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.1150G>C	p.Asp384His	missense_variant	3/5	1	NM_001144074.3	ENSP00000268148.8		Q7L5Y6-1
ENSG00000173867	ENST00000649547.1 linkuse as main transcript	c.1150G>C	p.Asp384His	missense_variant	4/10			ENSP00000497509.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461578

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727072

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

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

Jan 24, 2024

The c.1183G>C (p.D395H) alteration is located in exon 4 (coding exon 3) of the DET1 gene. This alteration results from a G to C substitution at nucleotide position 1183, causing the aspartic acid (D) at amino acid position 395 to be replaced by a histidine (H). 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

0.24

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Benign

-0.090

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.19

.;.;.;T

Eigen

Benign

0.15

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.88

.;D;.;D

M_CAP

Benign

0.0036

MetaRNN

Benign

0.34

T;T;T;T

MetaSVM

Benign

-0.87

MutationAssessor

Benign

1.2

.;.;.;L

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-1.9

.;N;N;N

REVEL

Benign

0.17

Sift

Benign

0.14

.;T;T;T

Sift4G

Benign

0.15

.;T;T;T

Polyphen

0.0

.;.;.;B

Vest4

0.79, 0.78

MutPred

0.42

Gain of catalytic residue at L386 (P = 0.1393);.;.;Gain of catalytic residue at L386 (P = 0.1393);

MVP

0.13

MPC

0.29

ClinPred

0.55

GERP RS

5.9

Varity_R

0.29

gMVP

0.55

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