8-58416937-C-A

Variant names:

• chr8-58416937-C-A
• rs373559127
• NM_001077619.2:c.172C>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001077619.2(UBXN2B):​c.172C>A​(p.Arg58Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,452,240 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: UBXN2B NM_001077619.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.900
• 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.059).
• BP7: Synonymous conserved (PhyloP=0.9 with no splicing effect.

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.172C>A	p.Arg58Arg	synonymous	Exon 2 of 8	NP_001071087.1	Q14CS0
	UBXN2B	NM_001363181.1		c.172C>A	p.Arg58Arg	synonymous	Exon 2 of 7	NP_001350110.1
	UBXN2B	NM_001330535.2		c.172C>A	p.Arg58Arg	synonymous	Exon 2 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.172C>A	p.Arg58Arg	synonymous	Exon 2 of 8	ENSP00000382507.2	Q14CS0
	UBXN2B	ENST00000970427.1		c.172C>A	p.Arg58Arg	synonymous	Exon 2 of 8	ENSP00000640486.1
	UBXN2B	ENST00000879981.1		c.172C>A	p.Arg58Arg	synonymous	Exon 2 of 7	ENSP00000550040.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1452240 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 722410

African (AFR) AF: 0.00 AC: 0 AN: 33290

American (AMR) AF: 0.00 AC: 0 AN: 44116

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25856

East Asian (EAS) AF: 0.00 AC: 0 AN: 39452

South Asian (SAS) AF: 0.00 AC: 0 AN: 85060

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52948

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5728

European-Non Finnish (NFE) AF: 9.04e-7 AC: 1 AN: 1105950

Other (OTH) AF: 0.00 AC: 0 AN: 59840

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.18
CADD	Benign	9.9
DANN	Benign	0.72
PhyloP100		0.90
PromoterAI		-0.010	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

dbSNP: rs373559127; hg19: chr8-59329496;