8-58416937-C-T

Variant names:

• chr8-58416937-C-T
• rs373559127
• NM_001077619.2:c.172C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001077619.2(UBXN2B):​c.172C>T​(p.Arg58Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000125 in 1,604,494 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: UBXN2B NM_001077619.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.900
• 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.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03537017).

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.172C>T	p.Arg58Trp	missense	Exon 2 of 8	NP_001071087.1	Q14CS0
	UBXN2B	NM_001363181.1		c.172C>T	p.Arg58Trp	missense	Exon 2 of 7	NP_001350110.1
	UBXN2B	NM_001330535.2		c.172C>T	p.Arg58Trp	missense	Exon 2 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.172C>T	p.Arg58Trp	missense	Exon 2 of 8	ENSP00000382507.2	Q14CS0
	UBXN2B	ENST00000970427.1		c.172C>T	p.Arg58Trp	missense	Exon 2 of 8	ENSP00000640486.1
	UBXN2B	ENST00000879981.1		c.172C>T	p.Arg58Trp	missense	Exon 2 of 7	ENSP00000550040.1

Frequencies

GnomAD3 genomes AF: 0.0000854 AC: 13 AN: 152138 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000146 AC: 36 AN: 246622 AF XY: 0.000194

Gnomad AFR exome AF: 0.0000653

Gnomad AMR exome AF: 0.0000298

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000801

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000129 AC: 187 AN: 1452238 Hom.: 0 Cov.: 31 AF XY: 0.000150 AC XY: 108 AN XY: 722408

African (AFR) AF: 0.00 AC: 0 AN: 33290

American (AMR) AF: 0.0000227 AC: 1 AN: 44116

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25856

East Asian (EAS) AF: 0.00 AC: 0 AN: 39452

South Asian (SAS) AF: 0.000893 AC: 76 AN: 85060

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52948

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5728

European-Non Finnish (NFE) AF: 0.0000922 AC: 102 AN: 1105950

Other (OTH) AF: 0.000134 AC: 8 AN: 59838

GnomAD4 genome AF: 0.0000854 AC: 13 AN: 152256 Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9 AN XY: 74458

African (AFR) AF: 0.0000481 AC: 2 AN: 41564

American (AMR) AF: 0.00 AC: 0 AN: 15290

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.0000675 Hom.: 0

Bravo AF: 0.0000378

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000122 AC: 1

ExAC AF: 0.000157 AC: 19

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.10
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Benign	0.058
Eigen_PC	Benign	0.092
FATHMM_MKL	Benign	0.64	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		0.90
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.16
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.010	D
Polyphen		1.0	D
Vest4		0.48
MVP		0.46
MPC		0.42
ClinPred		0.26	T
GERP RS		2.4
PromoterAI		-0.036	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.13
gMVP		0.50
Mutation Taster		=89/11	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: rs373559127; hg19: chr8-59329496;