11-5515273-T-G

Variant summary

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

The NM_145053.5(UBQLNL):c.1169A>C(p.Gln390Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: UBQLNL NM_145053.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.41

Genes affected

UBQLNL (HGNC:28294): (ubiquilin like) Predicted to enable polyubiquitin modification-dependent protein binding activity. Predicted to be involved in ubiquitin-dependent protein catabolic process. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

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/exons	MANE	UniProt
UBQLNL	NM_145053.5	c.1169A>C	p.Gln390Pro	missense_variant	1/1	ENST00000380184.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBQLNL	ENST00000380184.2	c.1169A>C	p.Gln390Pro	missense_variant	1/1		NM_145053.5	A2
UBQLNL	ENST00000673910.1	c.1139A>C	p.Gln380Pro	missense_variant	2/2			P4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251146 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135706

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: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 51

GnomAD4 genome Cov.: 33

Bravo AF: 0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 29, 2021

The c.1169A>C (p.Q390P) alteration is located in exon 1 (coding exon 1) of the UBQLNL gene. This alteration results from a A to C substitution at nucleotide position 1169, causing the glutamine (Q) at amino acid position 390 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Uncertain	0.015	T
BayesDel_noAF	Benign	-0.22
Cadd	Benign	18
Dann	Uncertain	0.99
DEOGEN2	Benign	0.0050	T
Eigen	Benign	0.18
Eigen_PC	Benign	0.041
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.0071	T
MetaRNN	Uncertain	0.63	D
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.0	L
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.76	N
REVEL	Benign	0.25
Sift	Benign	0.20	T
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.52
MutPred		0.55		Gain of phosphorylation at T389 (P = 0.0809);
MVP		0.46
MPC		0.082
ClinPred		0.53	D
GERP RS		4.1
Varity_R		0.25
gMVP		0.47

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: rs202095406; hg19: chr11-5536503;