chr8-58411426-G-C

Variant names:

• chr8-58411426-G-C
• NM_001077619.2:c.41G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001077619.2(UBXN2B):​c.41G>C​(p.Arg14Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000269 in 1,114,188 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: UBXN2B NM_001077619.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.634
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06981978).

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.41G>C	p.Arg14Thr	missense	Exon 1 of 8	NP_001071087.1	Q14CS0
	UBXN2B	NM_001363181.1		c.41G>C	p.Arg14Thr	missense	Exon 1 of 7	NP_001350110.1
	UBXN2B	NM_001330535.2		c.41G>C	p.Arg14Thr	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.41G>C	p.Arg14Thr	missense	Exon 1 of 8	ENSP00000382507.2	Q14CS0
	UBXN2B	ENST00000970427.1		c.41G>C	p.Arg14Thr	missense	Exon 1 of 8	ENSP00000640486.1
	UBXN2B	ENST00000879981.1		c.41G>C	p.Arg14Thr	missense	Exon 1 of 7	ENSP00000550040.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000269 AC: 3 AN: 1114188 Hom.: 0 Cov.: 31 AF XY: 0.00000566 AC XY: 3 AN XY: 530464

African (AFR) AF: 0.00 AC: 0 AN: 23090

American (AMR) AF: 0.00 AC: 0 AN: 8504

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14732

East Asian (EAS) AF: 0.00 AC: 0 AN: 26592

South Asian (SAS) AF: 0.00 AC: 0 AN: 28896

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2954

European-Non Finnish (NFE) AF: 0.00000322 AC: 3 AN: 932320

Other (OTH) AF: 0.00 AC: 0 AN: 44512

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	15
DANN	Benign	0.53
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.065	D
MetaRNN	Benign	0.070	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.63
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	0.39	N
REVEL	Benign	0.038
Sift	Benign	0.19	T
Sift4G	Benign	0.60	T
Polyphen		0.037	B
Vest4		0.25
MutPred		0.14		Gain of phosphorylation at R14 (P = 0.0069)
MVP		0.092
MPC		0.12
ClinPred		0.10	T
GERP RS		1.5
PromoterAI		0.048	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.087
gMVP		0.39
Mutation Taster		=96/4	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

hg19: chr8-59323985;