Genetic Variant DTX1:p.Ser306Arg (chr12-113078082-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_004416.3(DTX1):c.918C>G(p.Ser306Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000215 in 1,397,682 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: 31)

Exomes 𝑓: 0.0000016 ( 0 hom. )

Consequence

DTX1
NM_004416.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0590

Variant links:

Genes affected

DTX1 (HGNC:3060): (deltex E3 ubiquitin ligase 1) Studies in Drosophila have identified this gene as encoding a positive regulator of the Notch-signaling pathway. The human gene encodes a protein of unknown function; however, it may play a role in basic helix-loop-helix transcription factor activity. [provided by RefSeq, Jul 2008]

DTX1 links:

Genome browser will be placed here

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=0.19488305).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DTX1	NM_004416.3 link	c.918C>G	p.Ser306Arg	missense_variant	Exon 3 of 10	ENST00000548759.2	NP_004407.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DTX1	ENST00000548759.2 link	c.918C>G	p.Ser306Arg	missense_variant	Exon 3 of 10	2	NM_004416.3	ENSP00000510707.1		Q86Y01
DTX1	ENST00000257600.3 link	c.918C>G	p.Ser306Arg	missense_variant	Exon 2 of 9	1		ENSP00000257600.3		Q86Y01

Frequencies

GnomAD3 genomes

AF:

0.00000661

AC:

AN:

151260

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:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000160

AC:

AN:

1246422

Hom.:

Cov.:

AF XY:

0.00000327

AC XY:

AN XY:

611428

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000198

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000661

AC:

AN:

151260

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

73834

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:

0.0000148

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000224

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 14, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.918C>G (p.S306R) alteration is located in exon 2 (coding exon 2) of the DTX1 gene. This alteration results from a C to G substitution at nucleotide position 918, causing the serine (S) at amino acid position 306 to be replaced by an arginine (R). 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

Pathogenic

0.68

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.47

M_CAP

Benign

0.028

MetaRNN

Benign

0.19

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-1.3

REVEL

Benign

0.050

Sift

Benign

0.22

Sift4G

Benign

0.26

Polyphen

0.85

Vest4

0.24

MutPred

0.36

Gain of catalytic residue at R308 (P = 0.0081);

MVP

0.45

ClinPred

0.36

GERP RS

2.6

Varity_R

0.062

gMVP

0.61

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