9-83664110-T-C

Position:

• chr9-83664110-T-C

Variant summary

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

The NM_013438.5(UBQLN1):​c.1449-67A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 1,517,758 control chromosomes in the GnomAD database, including 101,084 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 0.35 (9513 hom., cov: 32)
  • Exomes 𝑓: 0.36 (91571 hom.)
• Consequence: UBQLN1 NM_013438.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.643

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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBQLN1	NM_013438.5	c.1449-67A>G		intron_variant		ENST00000376395.9	NP_038466.2
UBQLN1	NM_053067.3	c.1365-67A>G		intron_variant			NP_444295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBQLN1	ENST00000376395.9	c.1449-67A>G		intron_variant		1	NM_013438.5	ENSP00000365576.4

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52686 AN: 151944 Hom.: 9519 Cov.: 32

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.474

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.435

Gnomad EAS AF: 0.0329

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.369

GnomAD4 exome AF: 0.359 AC: 490444 AN: 1365696 Hom.: 91571 AF XY: 0.360 AC XY: 243411 AN XY: 676296

Gnomad4 AFR exome AF: 0.367

Gnomad4 AMR exome AF: 0.206

Gnomad4 ASJ exome AF: 0.425

Gnomad4 EAS exome AF: 0.0340

Gnomad4 SAS exome AF: 0.371

Gnomad4 FIN exome AF: 0.330

Gnomad4 NFE exome AF: 0.374

Gnomad4 OTH exome AF: 0.358

GnomAD4 genome AF: 0.347 AC: 52694 AN: 152062 Hom.: 9513 Cov.: 32 AF XY: 0.340 AC XY: 25308 AN XY: 74338

Gnomad4 AFR AF: 0.364

Gnomad4 AMR AF: 0.270

Gnomad4 ASJ AF: 0.435

Gnomad4 EAS AF: 0.0328

Gnomad4 SAS AF: 0.349

Gnomad4 FIN AF: 0.336

Gnomad4 NFE AF: 0.371

Gnomad4 OTH AF: 0.363

Alfa AF: 0.350 Hom.: 1510

Bravo AF: 0.342

Asia WGS AF: 0.197 AC: 688 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.3
DANN	Benign	0.63

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: rs2781002; hg19: chr9-86279025;