9-83666280-A-G

Position:

• chr9-83666280-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013438.5(UBQLN1):​c.1332+70T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 1,480,400 control chromosomes in the GnomAD database, including 28,218 homozygotes. 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: 𝑓 0.20 (3167 hom., cov: 32)
  • Exomes 𝑓: 0.19 (25051 hom.)
• Consequence: UBQLN1 NM_013438.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0850

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBQLN1	NM_013438.5	c.1332+70T>C		intron_variant		ENST00000376395.9	NP_038466.2
UBQLN1	NM_053067.3	c.1249-1135T>C		intron_variant			NP_444295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBQLN1	ENST00000376395.9	c.1332+70T>C		intron_variant		1	NM_013438.5	ENSP00000365576.4
UBQLN1	ENST00000257468.11	c.1249-1135T>C		intron_variant		1		ENSP00000257468.7
UBQLN1	ENST00000533705.5	n.3801+70T>C		intron_variant		1
UBQLN1	ENST00000526134.1	c.150+70T>C		intron_variant		3		ENSP00000436912.1

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29821 AN: 152056 Hom.: 3167 Cov.: 32

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.186

GnomAD4 exome AF: 0.187 AC: 247769 AN: 1328226 Hom.: 25051 AF XY: 0.190 AC XY: 126679 AN XY: 667962

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.0992

Gnomad4 ASJ exome AF: 0.181

Gnomad4 EAS exome AF: 0.000437

Gnomad4 SAS exome AF: 0.261

Gnomad4 FIN exome AF: 0.183

Gnomad4 NFE exome AF: 0.189

Gnomad4 OTH exome AF: 0.189

GnomAD4 genome AF: 0.196 AC: 29829 AN: 152174 Hom.: 3167 Cov.: 32 AF XY: 0.195 AC XY: 14486 AN XY: 74392

Gnomad4 AFR AF: 0.247

Gnomad4 AMR AF: 0.139

Gnomad4 ASJ AF: 0.177

Gnomad4 EAS AF: 0.00173

Gnomad4 SAS AF: 0.231

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.189

Gnomad4 OTH AF: 0.183

Alfa AF: 0.184 Hom.: 4399

Bravo AF: 0.193

Asia WGS AF: 0.0960 AC: 334 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	15
DANN	Benign	0.80
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

LitVar

Other links and lift over

dbSNP: rs12344615; hg19: chr9-86281195;