rs10501376

Positions:

• chr11-59204293-C-G

Variant summary

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

The NM_015177.2(DTX4):​c.1627-383C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0922 in 152,222 control chromosomes in the GnomAD database, including 946 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 0.092 (946 hom., cov: 32)
• Consequence: DTX4 NM_015177.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27

Genes affected

DTX4 (HGNC:29151): (deltex E3 ubiquitin ligase 4) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in Notch signaling pathway and protein ubiquitination. Predicted to be located in cytosol. Predicted to be active in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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 = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DTX4	NM_015177.2	c.1627-383C>G		intron_variant		ENST00000227451.4	NP_055992.1
DTX4	NM_001300727.2	c.1309-383C>G		intron_variant			NP_001287656.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DTX4	ENST00000227451.4	c.1627-383C>G		intron_variant		1	NM_015177.2	ENSP00000227451	P1
DTX4	ENST00000532982.5	c.1309-383C>G		intron_variant		1		ENSP00000434055
DTX4	ENST00000527475.1	n.569-383C>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0923 AC: 14035 AN: 152104 Hom.: 948 Cov.: 32

Gnomad AFR AF: 0.0234

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.0675

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.289

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.0884

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.101

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

GnomAD4 genome AF: 0.0922 AC: 14030 AN: 152222 Hom.: 946 Cov.: 32 AF XY: 0.0920 AC XY: 6846 AN XY: 74430

Gnomad4 AFR AF: 0.0234

Gnomad4 AMR AF: 0.0674

Gnomad4 ASJ AF: 0.146

Gnomad4 EAS AF: 0.288

Gnomad4 SAS AF: 0.148

Gnomad4 FIN AF: 0.0884

Gnomad4 NFE AF: 0.118

Gnomad4 OTH AF: 0.102

Alfa AF: 0.104 Hom.: 129

Bravo AF: 0.0888

Asia WGS AF: 0.186 AC: 650 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	0.083
DANN	Benign	0.52

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

LitVar

Other links and lift over

dbSNP: rs10501376; hg19: chr11-58971766;