10-58366117-C-T

Variant names:

• chr10-58366117-C-T
• rs11006122
• NM_003338.5:c.304+1241C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003338.5(UBE2D1):​c.304+1241C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 152,028 control chromosomes in the GnomAD database, including 15,578 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 0.45 (15578 hom., cov: 33)
• Consequence: UBE2D1 NM_003338.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.00
• Publications: 7 publications found

Genes affected

UBE2D1 (HGNC:12474): (ubiquitin conjugating enzyme E2 D1) The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation. Ubiquitination involves at least three classes of enzymes: ubiquitin-activating enzymes, or E1s, ubiquitin-conjugating enzymes, or E2s, and ubiquitin-protein ligases, or E3s. This gene encodes a member of the E2 ubiquitin-conjugating enzyme family. This enzyme is closely related to a stimulator of iron transport (SFT), and is up-regulated in hereditary hemochromatosis. It also functions in the ubiquitination of the tumor-suppressor protein p53 and the hypoxia-inducible transcription factor HIF1alpha by interacting with the E1 ubiquitin-activating enzyme and the E3 ubiquitin-protein ligases. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003338.5. 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
	UBE2D1	NM_003338.5	MANE Select	c.304+1241C>T		intron	N/A	NP_003329.1
	UBE2D1	NM_001204880.2		c.190+1241C>T		intron	N/A	NP_001191809.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBE2D1	ENST00000373910.9	TSL:1 MANE Select	c.304+1241C>T		intron	N/A	ENSP00000363019.3
	UBE2D1	ENST00000909472.1		c.304+1241C>T		intron	N/A	ENSP00000579531.1
	UBE2D1	ENST00000909473.1		c.226+1241C>T		intron	N/A	ENSP00000579532.1

Frequencies

GnomAD3 genomes AF: 0.448 AC: 68029 AN: 151910 Hom.: 15551 Cov.: 33

Gnomad AFR AF: 0.556

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.449

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.463

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

GnomAD4 genome AF: 0.448 AC: 68106 AN: 152028 Hom.: 15578 Cov.: 33 AF XY: 0.444 AC XY: 32997 AN XY: 74298

African (AFR) AF: 0.557 AC: 23089 AN: 41484

American (AMR) AF: 0.386 AC: 5906 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 1842 AN: 3466

East Asian (EAS) AF: 0.449 AC: 2313 AN: 5154

South Asian (SAS) AF: 0.406 AC: 1957 AN: 4818

European-Finnish (FIN) AF: 0.356 AC: 3765 AN: 10562

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.408 AC: 27717 AN: 67940

Other (OTH) AF: 0.459 AC: 963 AN: 2100

Alfa AF: 0.422 Hom.: 2270

Bravo AF: 0.458

Asia WGS AF: 0.394 AC: 1373 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.11
DANN	Benign	0.50
PhyloP100		-2.0
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

Other links and lift over

dbSNP: rs11006122; hg19: chr10-60125877;