chr9-83664110-T-C

Variant names:

• chr9-83664110-T-C
• rs2781002
• NM_013438.5:c.1449-67A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 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: Benign. The variant received -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.

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.1449-67A>G		intron	N/A	NP_038466.2
	UBQLN1	NM_053067.3		c.1365-67A>G		intron	N/A	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.1449-67A>G		intron	N/A	ENSP00000365576.4	Q9UMX0-1
	UBQLN1	ENST00000257468.11	TSL:1	c.1365-67A>G		intron	N/A	ENSP00000257468.7	Q9UMX0-2
	UBQLN1	ENST00000533705.5	TSL:1	n.3918-67A>G		intron	N/A

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

African (AFR) AF: 0.367 AC: 11080 AN: 30158

American (AMR) AF: 0.206 AC: 6783 AN: 32958

Ashkenazi Jewish (ASJ) AF: 0.425 AC: 9184 AN: 21614

East Asian (EAS) AF: 0.0340 AC: 1317 AN: 38758

South Asian (SAS) AF: 0.371 AC: 27677 AN: 74650

European-Finnish (FIN) AF: 0.330 AC: 16758 AN: 50830

Middle Eastern (MID) AF: 0.466 AC: 2303 AN: 4938

European-Non Finnish (NFE) AF: 0.374 AC: 395147 AN: 1055388

Other (OTH) AF: 0.358 AC: 20195 AN: 56402

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

African (AFR) AF: 0.364 AC: 15110 AN: 41468

American (AMR) AF: 0.270 AC: 4136 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.435 AC: 1512 AN: 3472

East Asian (EAS) AF: 0.0328 AC: 170 AN: 5184

South Asian (SAS) AF: 0.349 AC: 1685 AN: 4828

European-Finnish (FIN) AF: 0.336 AC: 3546 AN: 10564

Middle Eastern (MID) AF: 0.493 AC: 143 AN: 290

European-Non Finnish (NFE) AF: 0.371 AC: 25196 AN: 67940

Other (OTH) AF: 0.363 AC: 765 AN: 2106

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.3
DANN	Benign	0.63
PhyloP100		0.64
Mutation Taster		=100/0	polymorphism (auto)

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: rs2781002; hg19: chr9-86279025;