NM_001077619.2:c.24G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_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. 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: š‘“ 0.000013 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000063 ( 0 hom. )

Consequence

UBXN2B
NM_001077619.2 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.23
Variant links:
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]

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ACMG classification

Classification made for transcript

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
UBXN2BNM_001077619.2 linkc.24G>C p.Glu8Asp missense_variant Exon 1 of 8 ENST00000399598.7 NP_001071087.1 Q14CS0
UBXN2BNM_001363181.1 linkc.24G>C p.Glu8Asp missense_variant Exon 1 of 7 NP_001350110.1
UBXN2BNM_001330535.2 linkc.24G>C p.Glu8Asp missense_variant Exon 1 of 6 NP_001317464.1 Q14CS0E5RJ36
UBXN2BNR_156456.1 linkn.49G>C non_coding_transcript_exon_variant Exon 1 of 9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
UBXN2BENST00000399598.7 linkc.24G>C p.Glu8Asp missense_variant Exon 1 of 8 1 NM_001077619.2 ENSP00000382507.2 Q14CS0
UBXN2BENST00000520732.5 linkn.24G>C non_coding_transcript_exon_variant Exon 1 of 6 3 ENSP00000427759.1 E5RGJ4
UBXN2BENST00000522978.1 linkn.51G>C non_coding_transcript_exon_variant Exon 1 of 7 3
UBXN2BENST00000523409.5 linkn.24G>C non_coding_transcript_exon_variant Exon 1 of 9 5 ENSP00000428314.1 E5RJ36

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152180
Hom.:
0
Cov.:
32
show subpopulations
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
show subpopulations
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
show subpopulations
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

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