8-58447486-G-A

Variant names:

• chr8-58447486-G-A
• rs755047392
• NM_001077619.2:c.931G>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001077619.2(UBXN2B):​c.931G>A​(p.Asp311Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D311H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: UBXN2B NM_001077619.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.90
• 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: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.785

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.931G>A	p.Asp311Asn	missense	Exon 8 of 8	NP_001071087.1	Q14CS0
	UBXN2B	NM_001363181.1		c.793G>A	p.Asp265Asn	missense	Exon 7 of 7	NP_001350110.1
	UBXN2B	NR_156456.1		n.1047G>A		non_coding_transcript_exon	Exon 9 of 9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBXN2B	ENST00000399598.7	TSL:1 MANE Select	c.931G>A	p.Asp311Asn	missense	Exon 8 of 8	ENSP00000382507.2	Q14CS0
	UBXN2B	ENST00000970427.1		c.919G>A	p.Asp307Asn	missense	Exon 8 of 8	ENSP00000640486.1
	UBXN2B	ENST00000879981.1		c.847G>A	p.Asp283Asn	missense	Exon 7 of 7	ENSP00000550040.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.089	T
BayesDel_noAF	Benign	-0.37
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.31	T
Eigen	Pathogenic	0.88
Eigen_PC	Pathogenic	0.90
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.026	D
MetaRNN	Pathogenic	0.79	D
MetaSVM	Benign	-0.58	T
MutationAssessor	Benign	1.9	L
PhyloP100		8.9
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.34
Sift	Benign	0.086	T
Sift4G	Benign	0.064	T
Polyphen		1.0	D
Vest4		0.66
MutPred		0.62		Gain of ubiquitination at K307 (P = 0.1204)
MVP		0.80
MPC		0.45
ClinPred		0.97	D
GERP RS		6.1
Varity_R		0.17
gMVP		0.40
Mutation Taster		=69/31	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: rs755047392; hg19: chr8-59360045;