17-48911235-C-T

Variant names:

• chr17-48911235-C-T
• rs46522
• NM_023079.5:c.390+355C>T

Variant summary

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

The NM_023079.5(UBE2Z):​c.390+355C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 224,654 control chromosomes in the GnomAD database, including 25,066 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 0.41 (15404 hom., cov: 32)
  • Exomes 𝑓: 0.50 (9662 hom.)
• Consequence: UBE2Z NM_023079.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.395
• Publications: 129 publications found

Genes affected

UBE2Z (HGNC:25847): (ubiquitin conjugating enzyme E2 Z) This gene encodes an enzyme which ubiquitinates proteins which participate in signaling pathways and apoptosis. [provided by RefSeq, Feb 2012]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.69 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_023079.5. 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
	UBE2Z	NM_023079.5	MANE Select	c.390+355C>T		intron	N/A	NP_075567.2	Q9H832-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBE2Z	ENST00000360943.10	TSL:1 MANE Select	c.390+355C>T		intron	N/A	ENSP00000354201.5	Q9H832-1
	UBE2Z	ENST00000971025.1		c.390+355C>T		intron	N/A	ENSP00000641084.1
	UBE2Z	ENST00000882294.1		c.390+355C>T		intron	N/A	ENSP00000552353.1

Frequencies

GnomAD3 genomes AF: 0.412 AC: 62570 AN: 151834 Hom.: 15410 Cov.: 32

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.584

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.508

Gnomad EAS AF: 0.710

Gnomad SAS AF: 0.506

Gnomad FIN AF: 0.543

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.524

Gnomad OTH AF: 0.437

GnomAD4 exome AF: 0.498 AC: 36210 AN: 72702 Hom.: 9662 Cov.: 0 AF XY: 0.502 AC XY: 19209 AN XY: 38294

African (AFR) AF: 0.113 AC: 402 AN: 3572

American (AMR) AF: 0.429 AC: 2336 AN: 5442

Ashkenazi Jewish (ASJ) AF: 0.507 AC: 1108 AN: 2186

East Asian (EAS) AF: 0.706 AC: 3723 AN: 5276

South Asian (SAS) AF: 0.465 AC: 3592 AN: 7730

European-Finnish (FIN) AF: 0.531 AC: 1171 AN: 2206

Middle Eastern (MID) AF: 0.500 AC: 142 AN: 284

European-Non Finnish (NFE) AF: 0.518 AC: 21801 AN: 42108

Other (OTH) AF: 0.496 AC: 1935 AN: 3898

GnomAD4 genome AF: 0.412 AC: 62559 AN: 151952 Hom.: 15404 Cov.: 32 AF XY: 0.415 AC XY: 30836 AN XY: 74274

African (AFR) AF: 0.132 AC: 5484 AN: 41438

American (AMR) AF: 0.412 AC: 6296 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.508 AC: 1762 AN: 3470

East Asian (EAS) AF: 0.709 AC: 3663 AN: 5164

South Asian (SAS) AF: 0.506 AC: 2435 AN: 4816

European-Finnish (FIN) AF: 0.543 AC: 5727 AN: 10552

Middle Eastern (MID) AF: 0.455 AC: 133 AN: 292

European-Non Finnish (NFE) AF: 0.524 AC: 35598 AN: 67934

Other (OTH) AF: 0.441 AC: 931 AN: 2112

Alfa AF: 0.501 Hom.: 67236

Bravo AF: 0.393

Asia WGS AF: 0.551 AC: 1914 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.4
DANN	Benign	0.74
PhyloP100		-0.40
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: rs46522; hg19: chr17-46988597;