rs547889730

Variant names:

• chr9-83707620-G-C
• rs547889730
• NM_013438.5:c.60C>G

Your query was ambiguous. Multiple possible variants found:

• chr9-83707620-G-C
• chr9-83707620-G-T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_013438.5(UBQLN1):​c.60C>G​(p.Ala20Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000126 in 1,583,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: UBQLN1 NM_013438.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.457
• Publications: 0 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-AS1 (HGNC:55518): (UBQLN1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 9-83707620-G-C is Benign according to our data. Variant chr9-83707620-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 739713.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.457 with no splicing effect.
• BS2: High AC in GnomAd4 at 5 AD gene.

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.60C>G	p.Ala20Ala	synonymous	Exon 1 of 11	NP_038466.2
	UBQLN1	NM_053067.3		c.60C>G	p.Ala20Ala	synonymous	Exon 1 of 10	NP_444295.1	Q9UMX0-2
	UBQLN1-AS1	NR_135839.1		n.-215G>C		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBQLN1	ENST00000376395.9	TSL:1 MANE Select	c.60C>G	p.Ala20Ala	synonymous	Exon 1 of 11	ENSP00000365576.4	Q9UMX0-1
	UBQLN1	ENST00000257468.11	TSL:1	c.60C>G	p.Ala20Ala	synonymous	Exon 1 of 10	ENSP00000257468.7	Q9UMX0-2
	UBQLN1	ENST00000858201.1		c.60C>G	p.Ala20Ala	synonymous	Exon 1 of 12	ENSP00000528260.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152164 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000105 AC: 15 AN: 1431550 Hom.: 0 Cov.: 31 AF XY: 0.00000986 AC XY: 7 AN XY: 709932

African (AFR) AF: 0.000154 AC: 5 AN: 32516

American (AMR) AF: 0.00 AC: 0 AN: 40184

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25464

East Asian (EAS) AF: 0.00 AC: 0 AN: 38264

South Asian (SAS) AF: 0.0000121 AC: 1 AN: 82986

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49734

Middle Eastern (MID) AF: 0.000532 AC: 3 AN: 5644

European-Non Finnish (NFE) AF: 0.00000273 AC: 3 AN: 1097548

Other (OTH) AF: 0.0000507 AC: 3 AN: 59210

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152282 Hom.: 0 Cov.: 32 AF XY: 0.0000671 AC XY: 5 AN XY: 74464

African (AFR) AF: 0.000120 AC: 5 AN: 41556

American (AMR) AF: 0.00 AC: 0 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	17
DANN	Benign	0.93
PhyloP100		0.46
PromoterAI		0.081	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs547889730; hg19: chr9-86322535;