dbSNP rs1419697354: DTX1:p.Pro237Thr (chr12-113077873-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004416.3(DTX1):c.709C>A(p.Pro237Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000865 in 1,155,532 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P237S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 8.7e-7 ( 0 hom. )

Consequence

DTX1
NM_004416.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.45

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08425).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004416.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DTX1	NM_004416.3	MANE Select	c.709C>A	p.Pro237Thr	missense	Exon 3 of 10	NP_004407.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DTX1	ENST00000548759.2	TSL:2 MANE Select	c.709C>A	p.Pro237Thr	missense	Exon 3 of 10	ENSP00000510707.1	Q86Y01
DTX1	ENST00000257600.3	TSL:1	c.709C>A	p.Pro237Thr	missense	Exon 2 of 9	ENSP00000257600.3	Q86Y01
DTX1	ENST00000929430.1		c.709C>A	p.Pro237Thr	missense	Exon 3 of 9	ENSP00000599489.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.65e-7

AC:

AN:

1155532

Hom.:

Cov.:

AF XY:

0.00000179

AC XY:

AN XY:

559398

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

22728

American (AMR)

AF:

0.00

AC:

AN:

8628

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15126

East Asian (EAS)

AF:

0.00

AC:

AN:

25714

South Asian (SAS)

AF:

0.0000262

AC:

AN:

38236

European-Finnish (FIN)

AF:

0.00

AC:

AN:

25790

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3110

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

969490

Other (OTH)

AF:

0.00

AC:

AN:

46710

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Benign

0.55

DEOGEN2

Benign

0.17

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.36

M_CAP

Benign

0.067

MetaRNN

Benign

0.084

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.4

PhyloP100

1.4

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-0.28

REVEL

Benign

0.035

Sift

Benign

0.57

Sift4G

Benign

0.72

Polyphen

0.020

Vest4

0.20

MutPred

0.35

Gain of catalytic residue at G239 (P = 0)

MVP

0.25

ClinPred

0.071

GERP RS

1.2

Varity_R

0.078

gMVP

0.32

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over