8-58411409-G-C

Variant names:

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

Variant summary

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

The NM_001077619.2(UBXN2B):​c.24G>C​(p.Glu8Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000708 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar. 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 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000063 (0 hom.)
• Consequence: UBXN2B NM_001077619.2 missense
• Clinical Significance: Not reported in ClinVar
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05925861).

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>C	p.Glu8Asp	missense	Exon 1 of 8	NP_001071087.1	Q14CS0
	UBXN2B	NM_001363181.1		c.24G>C	p.Glu8Asp	missense	Exon 1 of 7	NP_001350110.1
	UBXN2B	NM_001330535.2		c.24G>C	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>C	p.Glu8Asp	missense	Exon 1 of 8	ENSP00000382507.2	Q14CS0
	UBXN2B	ENST00000970427.1		c.24G>C	p.Glu8Asp	missense	Exon 1 of 8	ENSP00000640486.1
	UBXN2B	ENST00000879981.1		c.24G>C	p.Glu8Asp	missense	Exon 1 of 7	ENSP00000550040.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 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: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000626 AC: 7 AN: 1118030 Hom.: 0 Cov.: 31 AF XY: 0.00000375 AC XY: 2 AN XY: 533120

African (AFR) AF: 0.0000432 AC: 1 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: 0.00 AC: 0 AN: 26640

South Asian (SAS) AF: 0.0000330 AC: 1 AN: 30306

European-Finnish (FIN) AF: 0.000156 AC: 5 AN: 32088

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 934836

Other (OTH) AF: 0.00 AC: 0 AN: 44658

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152298 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 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: 0.00 AC: 0 AN: 5146

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4834

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10628

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68020

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

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

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	0.19
DANN	Benign	0.49
DEOGEN2	Benign	0.011	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0043	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	0.0080
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		0.11	T
GERP RS		-2.5
PromoterAI		-0.023	Neutral
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; COSMIC: COSV99073912;