9-83676253-G-T

Variant names:

• chr9-83676253-G-T
• rs2780995
• NM_013438.5:c.1105+1474C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013438.5(UBQLN1):​c.1105+1474C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.704 in 152,168 control chromosomes in the GnomAD database, including 38,555 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 0.70 (38555 hom., cov: 33)
• Consequence: UBQLN1 NM_013438.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.254
• Publications: 1 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.862 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBQLN1	NM_013438.5	c.1105+1474C>A		intron_variant	Intron 6 of 10	ENST00000376395.9	NP_038466.2
UBQLN1	NM_053067.3	c.1105+1474C>A		intron_variant	Intron 6 of 9		NP_444295.1
UBQLN1	XM_005251948.4	c.1105+1474C>A		intron_variant	Intron 6 of 7		XP_005252005.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBQLN1	ENST00000376395.9	c.1105+1474C>A		intron_variant	Intron 6 of 10	1	NM_013438.5	ENSP00000365576.4
UBQLN1	ENST00000257468.11	c.1105+1474C>A		intron_variant	Intron 6 of 9	1		ENSP00000257468.7
UBQLN1	ENST00000533705.5	n.823+1474C>A		intron_variant	Intron 5 of 8	1

Frequencies

GnomAD3 genomes AF: 0.704 AC: 107017 AN: 152050 Hom.: 38522 Cov.: 33

Gnomad AFR AF: 0.841

Gnomad AMI AF: 0.714

Gnomad AMR AF: 0.710

Gnomad ASJ AF: 0.701

Gnomad EAS AF: 0.883

Gnomad SAS AF: 0.734

Gnomad FIN AF: 0.588

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.620

Gnomad OTH AF: 0.724

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.704 AC: 107105 AN: 152168 Hom.: 38555 Cov.: 33 AF XY: 0.703 AC XY: 52323 AN XY: 74386

African (AFR) AF: 0.841 AC: 34942 AN: 41548

American (AMR) AF: 0.710 AC: 10862 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.701 AC: 2433 AN: 3470

East Asian (EAS) AF: 0.883 AC: 4581 AN: 5186

South Asian (SAS) AF: 0.734 AC: 3541 AN: 4824

European-Finnish (FIN) AF: 0.588 AC: 6204 AN: 10554

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.620 AC: 42155 AN: 67964

Other (OTH) AF: 0.723 AC: 1530 AN: 2116

Alfa AF: 0.537 Hom.: 1627

Bravo AF: 0.722

Asia WGS AF: 0.801 AC: 2784 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.0
DANN	Benign	0.48
PhyloP100		-0.25
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: rs2780995; hg19: chr9-86291168;