chr11-5515868-A-T

Variant names:

• chr11-5515868-A-T
• rs867061058
• NM_145053.5:c.574T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_145053.5(UBQLNL):​c.574T>A​(p.Trp192Arg) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: UBQLNL NM_145053.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00400
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.01800868).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBQLNL	NM_145053.5	c.574T>A	p.Trp192Arg	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.574T>A	p.Trp192Arg	missense_variant	Exon 1 of 1	6	NM_145053.5	ENSP00000369531.1
ENSG00000239920	ENST00000380259.7	n.*739+74957T>A		intron_variant	Intron 5 of 7	5		ENSP00000369609.3
UBQLNL	ENST00000673910.1	c.544T>A	p.Trp182Arg	missense_variant	Exon 2 of 2			ENSP00000501246.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 52

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.26
DANN	Benign	0.76
DEOGEN2	Benign	0.011	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.13	T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.018	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-2.7	N
PhyloP100		0.0040
PrimateAI	Benign	0.23	T
PROVEAN	Benign	6.2	N
REVEL	Benign	0.034
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.072
MutPred		0.43		Gain of disorder (P = 3e-04);
MVP		0.072
MPC		0.015
ClinPred		0.10	T
GERP RS		-2.5
Varity_R		0.030
gMVP		0.22
Mutation Taster		=98/2	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: rs867061058; hg19: chr11-5537098;