chr9-83677891-G-C

Variant names:

• chr9-83677891-G-C
• rs778447675
• NM_013438.5:c.941C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_013438.5(UBQLN1):​c.941C>G​(p.Thr314Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: UBQLN1 NM_013438.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.18

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBQLN1	NM_013438.5	c.941C>G	p.Thr314Arg	missense_variant	Exon 6 of 11	ENST00000376395.9	NP_038466.2
UBQLN1	NM_053067.3	c.941C>G	p.Thr314Arg	missense_variant	Exon 6 of 10		NP_444295.1
UBQLN1	XM_005251948.4	c.941C>G	p.Thr314Arg	missense_variant	Exon 6 of 8		XP_005252005.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBQLN1	ENST00000376395.9	c.941C>G	p.Thr314Arg	missense_variant	Exon 6 of 11	1	NM_013438.5	ENSP00000365576.4
UBQLN1	ENST00000257468.11	c.941C>G	p.Thr314Arg	missense_variant	Exon 6 of 10	1		ENSP00000257468.7
UBQLN1	ENST00000533705.5	n.659C>G		non_coding_transcript_exon_variant	Exon 5 of 9	1
UBQLN1	ENST00000529923.1	c.332C>G	p.Thr111Arg	missense_variant	Exon 3 of 3	2		ENSP00000434194.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251464 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135908

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461886 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727240

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Pathogenic	0.40	D
BayesDel_noAF	Pathogenic	0.34
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.50	D;.;T
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D;T;D
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.68	D;D;D
MetaSVM	Uncertain	0.34	D
MutationAssessor	Pathogenic	3.1	M;M;.
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-3.7	D;D;D
REVEL	Uncertain	0.62
Sift	Benign	0.042	D;D;D
Sift4G	Uncertain	0.049	D;D;T
Polyphen		1.0	D;P;.
Vest4		0.78
MutPred		0.24		Loss of phosphorylation at T314 (P = 0.0126);Loss of phosphorylation at T314 (P = 0.0126);.;
MVP		0.81
MPC		0.52
ClinPred		0.80	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.56
gMVP		0.87

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: rs778447675; hg19: chr9-86292806;