rs387906711

Positions:

• chrX-56565389-C-A
• chrX-56565389-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_013444.4(UBQLN2):​c.1516C>A​(p.Pro506Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 24)
• Consequence: UBQLN2 NM_013444.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 1.15

Genes affected

UBQLN2 (HGNC:12509): (ubiquilin 2) This gene encodes an ubiquitin-like protein (ubiquilin) that shares high degree of similarity with related products in yeast, rat and frog. Ubiquilins contain a 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 bind the ATPase domain of the Hsp70-like Stch protein. [provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant X-56565389-C-A is Pathogenic according to our data. Variant chrX-56565389-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 29952.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBQLN2	NM_013444.4	c.1516C>A	p.Pro506Thr	missense_variant	1/1	ENST00000338222.7	NP_038472.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBQLN2	ENST00000338222.7	c.1516C>A	p.Pro506Thr	missense_variant	1/1		NM_013444.4	ENSP00000345195	P1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 24

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Amyotrophic lateral sclerosis type 15 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Aug 21, 2011

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Benign	21
DANN	Benign	0.85
DEOGEN2	Benign	0.025	T
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.74	T
M_CAP	Uncertain	0.21	D
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	0.92	N
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	0.17	N
REVEL	Uncertain	0.51
Sift	Benign	0.26	T
Sift4G	Benign	0.11	T
Polyphen		0.052	B
Vest4		0.76
MutPred		0.33		Gain of glycosylation at P506 (P = 0.0037);
MVP		1.0
MPC		0.53
ClinPred		0.11	T
GERP RS		4.2
Varity_R		0.12
gMVP		0.81

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: rs387906711; hg19: chrX-56591822;