chr8-58411409-G-T

Variant names:

• chr8-58411409-G-T
• rs948427869
• NM_001077619.2:c.24G>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001077619.2(UBXN2B):​c.24G>T​(p.Glu8Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000362 in 1,270,328 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E8Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000038 (0 hom.)
• Consequence: UBXN2B NM_001077619.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.23
• Publications: 0 publications found

Genes affected

UBXN2B (HGNC:27035): (UBX domain protein 2B) Predicted to enable ubiquitin binding activity. Involved in establishment of mitotic spindle orientation; negative regulation of protein localization to centrosome; and positive regulation of mitotic centrosome separation. Predicted to be located in Golgi apparatus; endoplasmic reticulum; and spindle pole centrosome. Predicted to be active in cytosol and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.058622688).
• BP6: Variant 8-58411409-G-T is Benign according to our data. Variant chr8-58411409-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2382750.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001077619.2. 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
	UBXN2B	NM_001077619.2	MANE Select	c.24G>T	p.Glu8Asp	missense	Exon 1 of 8	NP_001071087.1	Q14CS0
	UBXN2B	NM_001363181.1		c.24G>T	p.Glu8Asp	missense	Exon 1 of 7	NP_001350110.1
	UBXN2B	NM_001330535.2		c.24G>T	p.Glu8Asp	missense	Exon 1 of 6	NP_001317464.1	E5RJ36

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBXN2B	ENST00000399598.7	TSL:1 MANE Select	c.24G>T	p.Glu8Asp	missense	Exon 1 of 8	ENSP00000382507.2	Q14CS0
	UBXN2B	ENST00000970427.1		c.24G>T	p.Glu8Asp	missense	Exon 1 of 8	ENSP00000640486.1
	UBXN2B	ENST00000879981.1		c.24G>T	p.Glu8Asp	missense	Exon 1 of 7	ENSP00000550040.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152180 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 6936 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000385 AC: 43 AN: 1118030 Hom.: 0 Cov.: 31 AF XY: 0.0000469 AC XY: 25 AN XY: 533120

African (AFR) AF: 0.000130 AC: 3 AN: 23124

American (AMR) AF: 0.00 AC: 0 AN: 8546

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14844

East Asian (EAS) AF: 0.000113 AC: 3 AN: 26640

South Asian (SAS) AF: 0.00 AC: 0 AN: 30306

European-Finnish (FIN) AF: 0.0000623 AC: 2 AN: 32088

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2988

European-Non Finnish (NFE) AF: 0.0000332 AC: 31 AN: 934836

Other (OTH) AF: 0.0000896 AC: 4 AN: 44658

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152298 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74482

African (AFR) AF: 0.00 AC: 0 AN: 41588

American (AMR) AF: 0.00 AC: 0 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5146

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000453

Asia WGS AF: 0.000289 AC: 1 AN: 3472

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.17
DANN	Benign	0.52
DEOGEN2	Benign	0.011	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0051	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		-2.2
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	0.020	N
REVEL	Benign	0.0090
Sift	Benign	0.50	T
Sift4G	Benign	0.58	T
Polyphen		0.0	B
Vest4		0.061
MutPred		0.19		Loss of loop (P = 0.0112)
MVP		0.43
MPC		0.074
ClinPred		0.091	T
GERP RS		-2.5
PromoterAI		0.075	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.050
gMVP		0.27
Mutation Taster		=98/2	polymorphism

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: rs948427869; hg19: chr8-59323968;