rs200008585

Variant names:

• chr8-58416952-C-A
• rs200008585
• NM_001077619.2:c.187C>A

Your query was ambiguous. Multiple possible variants found:

• chr8-58416952-C-A
• chr8-58416952-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4 BP7

The NM_001077619.2(UBXN2B):​c.187C>A​(p.Arg63Arg) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000209 in 1,437,674 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: UBXN2B NM_001077619.2 splice_region, synonymous
• Scores: Splicing: ADA: 0.04400
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.34
• 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 (REVEL=0.212).
• BP7: Synonymous conserved (PhyloP=2.34 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.187C>A	p.Arg63Arg	splice_region synonymous	Exon 2 of 8	NP_001071087.1	Q14CS0
	UBXN2B	NM_001363181.1		c.187C>A	p.Arg63Arg	splice_region synonymous	Exon 2 of 7	NP_001350110.1
	UBXN2B	NM_001330535.2		c.187C>A	p.Arg63Arg	splice_region 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.187C>A	p.Arg63Arg	splice_region synonymous	Exon 2 of 8	ENSP00000382507.2	Q14CS0
	UBXN2B	ENST00000970427.1		c.187C>A	p.Arg63Ser	missense splice_region	Exon 2 of 8	ENSP00000640486.1
	UBXN2B	ENST00000970428.1		c.187C>A	p.Arg63Ser	missense splice_region	Exon 2 of 7	ENSP00000640487.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000209 AC: 3 AN: 1437674 Hom.: 0 Cov.: 30 AF XY: 0.00000140 AC XY: 1 AN XY: 714934

African (AFR) AF: 0.00 AC: 0 AN: 32846

American (AMR) AF: 0.00 AC: 0 AN: 42302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25352

East Asian (EAS) AF: 0.00 AC: 0 AN: 39186

South Asian (SAS) AF: 0.00 AC: 0 AN: 82200

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5654

European-Non Finnish (NFE) AF: 0.00000273 AC: 3 AN: 1098592

Other (OTH) AF: 0.00 AC: 0 AN: 59134

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_noAF	Benign	-0.22
CADD	Benign	14
DANN	Uncertain	1.0
PhyloP100		2.3
PromoterAI		-0.014	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.044
dbscSNV1_RF	Benign	0.36
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: rs200008585; hg19: chr8-59329511;