rs944947

Variant names:

• chr9-83685149-T-C
• rs944947
• NM_013438.5:c.332+855A>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.332+855A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 139,570 control chromosomes in the GnomAD database, including 3,170 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 0.21 (3170 hom., cov: 31)
• Consequence: UBQLN1 NM_013438.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.56
• Publications: 3 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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBQLN1	NM_013438.5	c.332+855A>G		intron_variant	Intron 2 of 10	ENST00000376395.9	NP_038466.2
UBQLN1	NM_053067.3	c.332+855A>G		intron_variant	Intron 2 of 9		NP_444295.1
UBQLN1	XM_005251948.4	c.332+855A>G		intron_variant	Intron 2 of 7		XP_005252005.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBQLN1	ENST00000376395.9	c.332+855A>G		intron_variant	Intron 2 of 10	1	NM_013438.5	ENSP00000365576.4
UBQLN1	ENST00000257468.11	c.332+855A>G		intron_variant	Intron 2 of 9	1		ENSP00000257468.7
UBQLN1	ENST00000533705.5	n.50+855A>G		intron_variant	Intron 1 of 8	1
UBQLN1	ENST00000529923.1	c.103-6550A>G		intron_variant	Intron 1 of 2	2		ENSP00000434194.1

Frequencies

GnomAD3 genomes AF: 0.214 AC: 29819 AN: 139482 Hom.: 3170 Cov.: 31

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.381

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.00512

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.204

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

GnomAD4 genome AF: 0.214 AC: 29829 AN: 139570 Hom.: 3170 Cov.: 31 AF XY: 0.214 AC XY: 14491 AN XY: 67588

African (AFR) AF: 0.250 AC: 10261 AN: 40998

American (AMR) AF: 0.170 AC: 2128 AN: 12522

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 613 AN: 3270

East Asian (EAS) AF: 0.00515 AC: 9 AN: 1748

South Asian (SAS) AF: 0.271 AC: 1114 AN: 4106

European-Finnish (FIN) AF: 0.203 AC: 2050 AN: 10118

Middle Eastern (MID) AF: 0.241 AC: 70 AN: 290

European-Non Finnish (NFE) AF: 0.202 AC: 12868 AN: 63742

Other (OTH) AF: 0.203 AC: 388 AN: 1916

Alfa AF: 0.195 Hom.: 477

Bravo AF: 0.193

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.24
DANN	Benign	0.60
PhyloP100		-2.6
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: rs944947; hg19: chr9-86300064;