rs10501376

Variant names:

• chr11-59204293-C-G
• rs10501376
• NM_015177.2:c.1627-383C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015177.2. 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
	DTX4	NM_015177.2	MANE Select	c.1627-383C>G		intron	N/A	NP_055992.1	Q9Y2E6-1
	DTX4	NM_001300727.2		c.1309-383C>G		intron	N/A	NP_001287656.1	Q9Y2E6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DTX4	ENST00000227451.4	TSL:1 MANE Select	c.1627-383C>G		intron	N/A	ENSP00000227451.3	Q9Y2E6-1
	DTX4	ENST00000532982.5	TSL:1	c.1309-383C>G		intron	N/A	ENSP00000434055.1	Q9Y2E6-2
	DTX4	ENST00000527475.1	TSL:2	n.569-383C>G		intron	N/A

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

African (AFR) AF: 0.0234 AC: 971 AN: 41552

American (AMR) AF: 0.0674 AC: 1031 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.146 AC: 506 AN: 3472

East Asian (EAS) AF: 0.288 AC: 1495 AN: 5182

South Asian (SAS) AF: 0.148 AC: 711 AN: 4820

European-Finnish (FIN) AF: 0.0884 AC: 937 AN: 10604

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.118 AC: 8005 AN: 67972

Other (OTH) AF: 0.102 AC: 215 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.083
DANN	Benign	0.52
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10501376;

hg19: chr11-58971766;