chr8-58445966-T-C

Variant names:

• chr8-58445966-T-C
• NM_001077619.2:c.731T>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.731T>C​(p.Leu244Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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: 0.0000014 (0 hom.)
• Consequence: UBXN2B NM_001077619.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.13

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=0.18644309).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBXN2B	NM_001077619.2	c.731T>C	p.Leu244Pro	missense_variant	Exon 7 of 8	ENST00000399598.7	NP_001071087.1
UBXN2B	NM_001363181.1	c.593T>C	p.Leu198Pro	missense_variant	Exon 6 of 7		NP_001350110.1
UBXN2B	NR_156456.1	n.847T>C		non_coding_transcript_exon_variant	Exon 8 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBXN2B	ENST00000399598.7	c.731T>C	p.Leu244Pro	missense_variant	Exon 7 of 8	1	NM_001077619.2	ENSP00000382507.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460884 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726746

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: 0.00000180

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

Oct 25, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.731T>C (p.L244P) alteration is located in exon 7 (coding exon 7) of the UBXN2B gene. This alteration results from a T to C substitution at nucleotide position 731, causing the leucine (L) at amino acid position 244 to be replaced by a proline (P). 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	0.086
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.038	T
Eigen	Benign	0.094
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.070
Sift	Benign	0.15	T
Sift4G	Benign	0.19	T
Polyphen		0.80	P
Vest4		0.17
MutPred		0.40		Gain of disorder (P = 0.0091);
MVP		0.51
MPC		0.14
ClinPred		0.59	D
GERP RS		5.3
Varity_R		0.21
gMVP		0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr8-59358525;