Variant 11-59182077-C-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_015177.2(DTX4):c.550C>A(p.Pro184Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

DTX4
NM_015177.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.58

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:

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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=0.10377836).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
DTX4	NM_015177.2 linkuse as main transcript	c.550C>A	p.Pro184Thr	missense_variant	2/9	ENST00000227451.4	NP_055992.1
DTX4	NM_001300727.2 linkuse as main transcript	c.232C>A	p.Pro78Thr	missense_variant	2/9		NP_001287656.1
LOC124902675	XR_007062681.1 linkuse as main transcript	n.2649-2258G>T		intron_variant
LOC124902675	XR_007062682.1 linkuse as main transcript	n.2649-2258G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DTX4	ENST00000227451.4 linkuse as main transcript	c.550C>A	p.Pro184Thr	missense_variant	2/9	1	NM_015177.2	ENSP00000227451.3		Q9Y2E6-1
DTX4	ENST00000532982.5 linkuse as main transcript	c.232C>A	p.Pro78Thr	missense_variant	2/9	1		ENSP00000434055.1		Q9Y2E6-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459890

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726010

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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 03, 2024

The c.550C>A (p.P184T) alteration is located in exon 2 (coding exon 2) of the DTX4 gene. This alteration results from a C to A substitution at nucleotide position 550, causing the proline (P) at amino acid position 184 to be replaced by a threonine (T). 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

0.061

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

7.1

DANN

Benign

0.81

DEOGEN2

Benign

0.030

.;T

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.46

LIST_S2

Benign

0.47

T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.10

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.9

.;L

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.060

N;N

REVEL

Benign

0.026

Sift

Benign

0.22

T;T

Sift4G

Benign

0.61

T;T

Polyphen

0.025

.;B

Vest4

0.45

MutPred

0.19

.;Gain of phosphorylation at P184 (P = 0.0306);

MVP

0.30

MPC

0.36

ClinPred

0.18

GERP RS

3.5

Varity_R

0.032

gMVP

0.22

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