UBQLN1 p.Gly483Gly

Variant names:

• chr9-83664042-A-A
• NM_013438.5:c.

Your query was ambiguous. Multiple possible variants found:

• chr9-83664043--
• chr9-83664043-C-A
• chr9-83664043-C-G
• chr9-83664043-C-T

Variant summary

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

The NM_013438.5(UBQLN1):​c. variant causes a splice region, exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: UBQLN1 NM_013438.5 splice_region, exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0430
• Publications: 0 publications found

Genes affected

UBQLN1 (HGNC:12508): (ubiquilin 1) This gene encodes an ubiquitin-like protein (ubiquilin) that shares a high degree of similarity with related products in yeast, rat and frog. Ubiquilins contain an N-terminal ubiquitin-like domain and a C-terminal ubiquitin-associated domain. They physically associate with both proteasomes and ubiquitin ligases, and thus are thought to functionally link the ubiquitination machinery to the proteasome to affect in vivo protein degradation. This ubiquilin has also been shown to modulate accumulation of presenilin proteins, and it is found in lesions associated with Alzheimer's and Parkinson's disease. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

UBQLN1 Gene-Disease associations (from GenCC):

• intellectual disability

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013438.5. 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
	UBQLN1	NM_013438.5	MANE Select	c.		splice_region exon_region	Exon 10 of 11	NP_038466.2
	UBQLN1	NM_053067.3		c.		splice_region exon_region	Exon 9 of 10	NP_444295.1	Q9UMX0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBQLN1	ENST00000376395.9	TSL:1 MANE Select	c.		splice_region exon_region	Exon 10 of 11	ENSP00000365576.4	Q9UMX0-1
	UBQLN1	ENST00000257468.11	TSL:1	c.		splice_region exon_region	Exon 9 of 10	ENSP00000257468.7	Q9UMX0-2
	UBQLN1	ENST00000533705.5	TSL:1	n.		splice_region exon_region	Exon 8 of 9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.043

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr9-86278957;