11-5515511-G-T

Variant names:

• chr11-5515511-G-T
• NM_145053.5:c.931C>A

Variant summary

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

The NM_145053.5(UBQLNL):​c.931C>A​(p.Pro311Thr) 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: 1.57

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]

ENSG00000239920 (HGNC:):

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=0.06598979).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBQLNL	NM_145053.5	c.931C>A	p.Pro311Thr	missense_variant	Exon 1 of 1	ENST00000380184.2	NP_659490.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBQLNL	ENST00000380184.2	c.931C>A	p.Pro311Thr	missense_variant	Exon 1 of 1	6	NM_145053.5	ENSP00000369531.1
ENSG00000239920	ENST00000380259.7	n.*739+75314C>A		intron_variant	Intron 5 of 7	5		ENSP00000369609.3
UBQLNL	ENST00000673910.1	c.901C>A	p.Pro301Thr	missense_variant	Exon 2 of 2			ENSP00000501246.1

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

Dec 14, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.931C>A (p.P311T) alteration is located in exon 1 (coding exon 1) of the UBQLNL gene. This alteration results from a C to A substitution at nucleotide position 931, causing the proline (P) at amino acid position 311 to be replaced by a threonine (T). 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	0.065
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	0.74
DANN	Benign	0.47
DEOGEN2	Benign	0.0018	T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.093	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.066	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.86	N
REVEL	Benign	0.058
Sift	Benign	0.25	T
Sift4G	Benign	0.20	T
Polyphen		0.022	B
Vest4		0.25
MutPred		0.28		Gain of phosphorylation at P311 (P = 0.014);
MVP		0.26
MPC		0.015
ClinPred		0.18	T
GERP RS		0.89
Varity_R		0.040
gMVP		0.10

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: chr11-5536741;