12-113077841-C-T

Variant summary

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

The NM_004416.3(DTX1):​c.677C>T​(p.Ala226Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000252 in 1,189,252 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 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. A226E) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000025 ( 0 hom. )

Consequence

DTX1
NM_004416.3 missense

Scores

2
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.41
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]

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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=0.09998047).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DTX1NM_004416.3 linkc.677C>T p.Ala226Val missense_variant Exon 3 of 10 ENST00000548759.2 NP_004407.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DTX1ENST00000548759.2 linkc.677C>T p.Ala226Val missense_variant Exon 3 of 10 2 NM_004416.3 ENSP00000510707.1 Q86Y01
DTX1ENST00000257600.3 linkc.677C>T p.Ala226Val missense_variant Exon 2 of 9 1 ENSP00000257600.3 Q86Y01

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.00000252
AC:
3
AN:
1189252
Hom.:
0
Cov.:
33
AF XY:
0.00000173
AC XY:
1
AN XY:
578718
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.0000591
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000362
Gnomad4 NFE exome
AF:
0.00000101
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.062
BayesDel_addAF
Benign
-0.35
T
BayesDel_noAF
Benign
-0.74
CADD
Benign
21
DANN
Benign
0.89
DEOGEN2
Benign
0.17
T
Eigen
Benign
-0.74
Eigen_PC
Benign
-0.67
FATHMM_MKL
Benign
0.074
N
LIST_S2
Benign
0.40
T
M_CAP
Pathogenic
0.36
D
MetaRNN
Benign
0.10
T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
0.28
N
PrimateAI
Pathogenic
0.86
D
PROVEAN
Benign
-0.17
N
REVEL
Benign
0.039
Sift
Benign
0.63
T
Sift4G
Benign
0.51
T
Polyphen
0.0
B
Vest4
0.13
MutPred
0.23
Gain of catalytic residue at P230 (P = 5e-04);
MVP
0.27
ClinPred
0.20
T
GERP RS
2.1
Varity_R
0.055
gMVP
0.12

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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.

Other links and lift over

dbSNP: rs772328217; hg19: chr12-113515646; API