11-5515363-G-A

Variant names:

• chr11-5515363-G-A
• rs183094057
• NM_145053.5:c.1079C>T

Variant summary

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

The NM_145053.5(UBQLNL):​c.1079C>T​(p.Thr360Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000731 in 1,614,228 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00025 (1 hom., cov: 32)
  • Exomes 𝑓: 0.000055 (0 hom.)
• Consequence: UBQLNL NM_145053.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.399

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=0.017126083).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBQLNL	NM_145053.5	c.1079C>T	p.Thr360Ile	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.1079C>T	p.Thr360Ile	missense_variant	Exon 1 of 1	6	NM_145053.5	ENSP00000369531.1
ENSG00000239920	ENST00000380259.7	n.*739+75462C>T		intron_variant	Intron 5 of 7	5		ENSP00000369609.3
UBQLNL	ENST00000673910.1	c.1049C>T	p.Thr350Ile	missense_variant	Exon 2 of 2			ENSP00000501246.1

Frequencies

GnomAD3 genomes AF: 0.000250 AC: 38 AN: 152224 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.000955

GnomAD3 exomes AF: 0.000136 AC: 34 AN: 250882 Hom.: 0 AF XY: 0.000155 AC XY: 21 AN XY: 135546

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000318

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000163

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000124

Gnomad OTH exome AF: 0.000817

GnomAD4 exome AF: 0.0000547 AC: 80 AN: 1461886 Hom.: 0 Cov.: 92 AF XY: 0.0000633 AC XY: 46 AN XY: 727242

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000335

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.000126

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.0000441

Gnomad4 OTH exome AF: 0.0000993

GnomAD4 genome AF: 0.000249 AC: 38 AN: 152342 Hom.: 1 Cov.: 32 AF XY: 0.000309 AC XY: 23 AN XY: 74512

Gnomad4 AFR AF: 0.0000240

Gnomad4 AMR AF: 0.00157

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.000945

Alfa AF: 0.0000225 Hom.: 0

Bravo AF: 0.000359

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000165 AC: 20

Asia WGS AF: 0.000578 AC: 2 AN: 3476

EpiCase AF: 0.000164

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 29, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1079C>T (p.T360I) alteration is located in exon 1 (coding exon 1) of the UBQLNL gene. This alteration results from a C to T substitution at nucleotide position 1079, causing the threonine (T) at amino acid position 360 to be replaced by an isoleucine (I). 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	0.11
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	4.4
DANN	Benign	0.93
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.057	N
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.017	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.90	L
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.038
Sift	Uncertain	0.026	D
Sift4G	Uncertain	0.060	T
Polyphen		0.27	B
Vest4		0.11
MVP		0.34
MPC		0.016
ClinPred		0.030	T
GERP RS		1.9
Varity_R		0.043
gMVP		0.17

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: rs183094057; hg19: chr11-5536593;