11-5515433-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_145053.5(UBQLNL):c.1009G>C(p.Gly337Arg) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: UBQLNL NM_145053.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.04

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.031550735).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UBQLNL	NM_145053.5	c.1009G>C	p.Gly337Arg	missense_variant	1/1	ENST00000380184.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBQLNL	ENST00000380184.2	c.1009G>C	p.Gly337Arg	missense_variant	1/1		NM_145053.5	A2
UBQLNL	ENST00000673910.1	c.979G>C	p.Gly327Arg	missense_variant	2/2			P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 92

GnomAD4 genome Cov.: 32

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

May 24, 2023

The c.1009G>C (p.G337R) alteration is located in exon 1 (coding exon 1) of the UBQLNL gene. This alteration results from a G to C substitution at nucleotide position 1009, causing the glycine (G) at amino acid position 337 to be replaced by an arginine (R). 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	0.068
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
Cadd	Benign	0.0030
Dann	Benign	0.47
DEOGEN2	Benign	0.0048	T
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.00060	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.032	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.69	N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.17	T
PROVEAN	Benign	-0.91	N
REVEL	Benign	0.040
Sift	Benign	0.15	T
Sift4G	Benign	0.15	T
Polyphen		0.0	B
Vest4		0.067
MutPred		0.37		Gain of MoRF binding (P = 0.0039);
MVP		0.048
MPC		0.014
ClinPred		0.10	T
GERP RS		-8.5
Varity_R		0.057
gMVP		0.068

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-5536663;