rs755047392

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr8-58447486-G-A
• chr8-58447486-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

Verdict is Uncertain_significance. Variant got 3 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBXN2B	NM_001077619.2	c.931G>A	p.Asp311Asn	missense_variant	Exon 8 of 8	ENST00000399598.7	NP_001071087.1
UBXN2B	NM_001363181.1	c.793G>A	p.Asp265Asn	missense_variant	Exon 7 of 7		NP_001350110.1
UBXN2B	NR_156456.1	n.1047G>A		non_coding_transcript_exon_variant	Exon 9 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBXN2B	ENST00000399598.7	c.931G>A	p.Asp311Asn	missense_variant	Exon 8 of 8	1	NM_001077619.2	ENSP00000382507.2
UBXN2B	ENST00000523409.5	n.*431G>A		non_coding_transcript_exon_variant	Exon 9 of 9	5		ENSP00000428314.1
UBXN2B	ENST00000523409.5	n.*431G>A		3_prime_UTR_variant	Exon 9 of 9	5		ENSP00000428314.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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
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

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

Publications

LitVar

Other links and lift over

dbSNP: rs755047392; hg19: chr8-59360045;