8-58411426-G-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 14/21 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

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 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBXN2B	NM_001077619.2	c.41G>C	p.Arg14Thr	missense_variant	Exon 1 of 8	ENST00000399598.7	NP_001071087.1
UBXN2B	NM_001363181.1	c.41G>C	p.Arg14Thr	missense_variant	Exon 1 of 7		NP_001350110.1
UBXN2B	NM_001330535.2	c.41G>C	p.Arg14Thr	missense_variant	Exon 1 of 6		NP_001317464.1
UBXN2B	NR_156456.1	n.66G>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.41G>C	p.Arg14Thr	missense_variant	Exon 1 of 8	1	NM_001077619.2	ENSP00000382507.2
UBXN2B	ENST00000520732.5	n.41G>C		non_coding_transcript_exon_variant	Exon 1 of 6	3		ENSP00000427759.1
UBXN2B	ENST00000522978.1	n.68G>C		non_coding_transcript_exon_variant	Exon 1 of 7	3
UBXN2B	ENST00000523409.5	n.41G>C		non_coding_transcript_exon_variant	Exon 1 of 9	5		ENSP00000428314.1

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000322

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 30, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.41G>C (p.R14T) alteration is located in exon 1 (coding exon 1) of the UBXN2B gene. This alteration results from a G to C substitution at nucleotide position 41, causing the arginine (R) at amino acid position 14 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T
M_CAP	Benign	0.065	D
MetaRNN	Benign	0.070	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L;.
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);Gain of phosphorylation at R14 (P = 0.0069);
MVP		0.092
MPC		0.12
ClinPred		0.10	T
GERP RS		1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.087
gMVP		0.39

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-59323985;