Genetic Variant DTX1:p.Pro237Ser (chr12-113077873-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_004416.3(DTX1):c.709C>T(p.Pro237Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000153 in 1,304,766 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

DTX1
NM_004416.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.052166432).

BS2

High AC in GnomAdExome4 at 16 AD gene.

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>T	p.Pro237Ser	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>T	p.Pro237Ser	missense	Exon 3 of 10	ENSP00000510707.1	Q86Y01
DTX1	ENST00000257600.3	TSL:1	c.709C>T	p.Pro237Ser	missense	Exon 2 of 9	ENSP00000257600.3	Q86Y01
DTX1	ENST00000929430.1		c.709C>T	p.Pro237Ser	missense	Exon 3 of 9	ENSP00000599489.1

Frequencies

GnomAD3 genomes

AF:

0.0000268

AC:

AN:

149234

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:

0.0000595

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000249

AC:

AN:

4022

AF XY:

0.000385

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000486

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000138

AC:

AN:

1155532

Hom.:

Cov.:

AF XY:

0.0000143

AC XY:

AN XY:

559398

show subpopulations

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:

0.00

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:

0.0000155

AC:

AN:

969490

Other (OTH)

AF:

0.0000214

AC:

AN:

46710

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.544

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000268

AC:

AN:

149234

Hom.:

Cov.:

AF XY:

0.0000275

AC XY:

AN XY:

72796

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41058

American (AMR)

AF:

0.00

AC:

AN:

15028

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3452

East Asian (EAS)

AF:

0.00

AC:

AN:

5148

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9234

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000595

AC:

AN:

67206

Other (OTH)

AF:

0.00

AC:

AN:

2060

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.19

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.35

M_CAP

Benign

0.067

MetaRNN

Benign

0.052

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.81

PhyloP100

1.4

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-0.48

REVEL

Benign

0.042

Sift

Benign

0.63

Sift4G

Benign

0.81

Polyphen

0.0010

Vest4

0.18

MutPred

0.34

Gain of catalytic residue at G239 (P = 0)

MVP

0.076

ClinPred

0.042

GERP RS

1.2

Varity_R

0.066

gMVP

0.26

Mutation Taster

=98/2

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over