rs2384077

Positions:

• chr12-113066691-G-A
• chr12-113066691-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004416.3(DTX1):​c.259+8240G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.659 in 151,968 control chromosomes in the GnomAD database, including 33,323 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.66 (33323 hom., cov: 31)
• Consequence: DTX1 NM_004416.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.23

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.877 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DTX1	NM_004416.3	c.259+8240G>A		intron_variant		ENST00000548759.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DTX1	ENST00000548759.2	c.259+8240G>A		intron_variant		2	NM_004416.3	P1
DTX1	ENST00000257600.3	c.259+8240G>A		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.659 AC: 100126 AN: 151850 Hom.: 33315 Cov.: 31

Gnomad AFR AF: 0.697

Gnomad AMI AF: 0.693

Gnomad AMR AF: 0.633

Gnomad ASJ AF: 0.607

Gnomad EAS AF: 0.898

Gnomad SAS AF: 0.660

Gnomad FIN AF: 0.606

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.635

Gnomad OTH AF: 0.655

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.659 AC: 100178 AN: 151968 Hom.: 33323 Cov.: 31 AF XY: 0.658 AC XY: 48895 AN XY: 74282

Gnomad4 AFR AF: 0.696

Gnomad4 AMR AF: 0.633

Gnomad4 ASJ AF: 0.607

Gnomad4 EAS AF: 0.898

Gnomad4 SAS AF: 0.659

Gnomad4 FIN AF: 0.606

Gnomad4 NFE AF: 0.635

Gnomad4 OTH AF: 0.659

Alfa AF: 0.638 Hom.: 29007

Bravo AF: 0.665

Asia WGS AF: 0.771 AC: 2677 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	11
DANN	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs2384077; hg19: chr12-113504496;