NM_004416.3:c.862A>C

Variant names:

• chr12-113078026-A-C
• NM_004416.3:c.862A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004416.3(DTX1):​c.862A>C​(p.Thr288Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: DTX1 NM_004416.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.556
• Publications: 0 publications found

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]

ACMG classification

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=0.08409825).

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.862A>C	p.Thr288Pro	missense	Exon 3 of 10	NP_004407.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DTX1	ENST00000548759.2	TSL:2 MANE Select	c.862A>C	p.Thr288Pro	missense	Exon 3 of 10	ENSP00000510707.1	Q86Y01
	DTX1	ENST00000257600.3	TSL:1	c.862A>C	p.Thr288Pro	missense	Exon 2 of 9	ENSP00000257600.3	Q86Y01
	DTX1	ENST00000929430.1		c.862A>C	p.Thr288Pro	missense	Exon 3 of 9	ENSP00000599489.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.051
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	16
DANN	Benign	0.96
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.47	T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.084	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.20	N
PhyloP100		0.56
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	0.14	N
REVEL	Benign	0.027
Sift	Benign	0.26	T
Sift4G	Benign	0.30	T
Polyphen		0.072	B
Vest4		0.14
MutPred		0.29		Gain of catalytic residue at T288 (P = 0.0016)
MVP		0.30
ClinPred		0.10	T
GERP RS		0.38
Varity_R		0.10
gMVP		0.35
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

hg19: chr12-113515831;