8-58411409-G-C

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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

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 Likely_benign. Variant got -2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBXN2B	NM_001077619.2	c.24G>C	p.Glu8Asp	missense_variant	Exon 1 of 8	ENST00000399598.7	NP_001071087.1
UBXN2B	NM_001363181.1	c.24G>C	p.Glu8Asp	missense_variant	Exon 1 of 7		NP_001350110.1
UBXN2B	NM_001330535.2	c.24G>C	p.Glu8Asp	missense_variant	Exon 1 of 6		NP_001317464.1
UBXN2B	NR_156456.1	n.49G>C		non_coding_transcript_exon_variant	Exon 1 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBXN2B	ENST00000399598.7	c.24G>C	p.Glu8Asp	missense_variant	Exon 1 of 8	1	NM_001077619.2	ENSP00000382507.2
UBXN2B	ENST00000520732.5	n.24G>C		non_coding_transcript_exon_variant	Exon 1 of 6	3		ENSP00000427759.1
UBXN2B	ENST00000522978.1	n.51G>C		non_coding_transcript_exon_variant	Exon 1 of 7	3
UBXN2B	ENST00000523409.5	n.24G>C		non_coding_transcript_exon_variant	Exon 1 of 9	5		ENSP00000428314.1

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

Gnomad4 AFR exome AF: 0.0000432

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000330

Gnomad4 FIN exome AF: 0.000156

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152298 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74482

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.059	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L;.
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);Loss of loop (P = 0.0112);
MVP		0.43
MPC		0.074
ClinPred		0.11	T
GERP RS		-2.5
Varity_R		0.050
gMVP		0.27

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: rs948427869; hg19: chr8-59323968; COSMIC: COSV99073912;