chrX-56564023-G-T

Variant names:

• chrX-56564023-G-T
• rs1156273861
• NM_013444.4:c.150G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_013444.4(UBQLN2):​c.150G>T​(p.Glu50Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. E50E) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: UBQLN2 NM_013444.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.739
• Publications: 1 publications found

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]

UBQLN2 Gene-Disease associations (from GenCC):

• amyotrophic lateral sclerosis type 15

  Inheritance: XL Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Genomics England PanelApp, ClinGen, Labcorp Genetics (formerly Invitae)
• amyotrophic lateral sclerosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000298134 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1272).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013444.4. 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
	UBQLN2	NM_013444.4	MANE Select	c.150G>T	p.Glu50Asp	missense	Exon 1 of 1	NP_038472.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBQLN2	ENST00000338222.7	TSL:6 MANE Select	c.150G>T	p.Glu50Asp	missense	Exon 1 of 1	ENSP00000345195.5	Q9UHD9
	ENSG00000298134	ENST00000753204.1		n.148+108C>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1071233 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 348839

African (AFR) AF: 0.00 AC: 0 AN: 25766

American (AMR) AF: 0.00 AC: 0 AN: 30521

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18868

East Asian (EAS) AF: 0.00 AC: 0 AN: 28849

South Asian (SAS) AF: 0.00 AC: 0 AN: 51175

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38738

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4093

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 828102

Other (OTH) AF: 0.00 AC: 0 AN: 45121

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	19
DANN	Benign	0.94
DEOGEN2	Benign	0.095	T
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.74
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.21
Sift	Benign	0.46	T
Sift4G	Benign	0.79	T
Polyphen		0.021	B
Vest4		0.13
MutPred		0.30		Loss of sheet (P = 0.1158)
MVP		0.80
MPC		1.2
ClinPred		0.70	D
GERP RS		3.7
PromoterAI		-0.0098	Neutral
Varity_R		0.32
gMVP		0.81
Mutation Taster		=79/21	polymorphism

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: rs1156273861; hg19: chrX-56590456;