11-5515318-C-T

Variant names:

• chr11-5515318-C-T
• rs36020613
• NM_145053.5:c.1124G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_145053.5(UBQLNL):​c.1124G>A​(p.Arg375Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00222 in 1,614,172 control chromosomes in the GnomAD database, including 31 homozygotes. 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 Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0079 (11 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (20 hom.)
• Consequence: UBQLNL NM_145053.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0810
• Publications: 4 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0032996535).
• BP6: Variant 11-5515318-C-T is Benign according to our data. Variant chr11-5515318-C-T is described in ClinVar as Benign. ClinVar VariationId is 715486.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00793 (1208/152290) while in subpopulation AFR AF = 0.0238 (988/41564). AF 95% confidence interval is 0.0225. There are 11 homozygotes in GnomAd4. There are 575 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 11 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145053.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBQLNL	NM_145053.5	MANE Select	c.1124G>A	p.Arg375Gln	missense	Exon 1 of 1	NP_659490.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBQLNL	ENST00000380184.2	TSL:6 MANE Select	c.1124G>A	p.Arg375Gln	missense	Exon 1 of 1	ENSP00000369531.1	Q8IYU4-1
	ENSG00000239920	ENST00000380259.7	TSL:5	n.*739+75507G>A		intron	N/A	ENSP00000369609.3	A0A2U3TZJ3
	UBQLNL	ENST00000673910.1		c.1094G>A	p.Arg365Gln	missense	Exon 2 of 2	ENSP00000501246.1	A0A669KBE4

Frequencies

GnomAD3 genomes AF: 0.00789 AC: 1201 AN: 152172 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.0236

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00563

Gnomad ASJ AF: 0.0179

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000720

Gnomad OTH AF: 0.0100

GnomAD2 exomes AF: 0.00320 AC: 804 AN: 251006 AF XY: 0.00258

Gnomad AFR exome AF: 0.0242

Gnomad AMR exome AF: 0.00309

Gnomad ASJ exome AF: 0.0177

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000821

Gnomad OTH exome AF: 0.00376

GnomAD4 exome AF: 0.00163 AC: 2381 AN: 1461882 Hom.: 20 Cov.: 92 AF XY: 0.00156 AC XY: 1135 AN XY: 727240

African (AFR) AF: 0.0255 AC: 855 AN: 33480

American (AMR) AF: 0.00364 AC: 163 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0187 AC: 488 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000209 AC: 18 AN: 86256

European-Finnish (FIN) AF: 0.000168 AC: 9 AN: 53418

Middle Eastern (MID) AF: 0.00641 AC: 37 AN: 5768

European-Non Finnish (NFE) AF: 0.000509 AC: 566 AN: 1112006

Other (OTH) AF: 0.00406 AC: 245 AN: 60396

GnomAD4 genome AF: 0.00793 AC: 1208 AN: 152290 Hom.: 11 Cov.: 32 AF XY: 0.00772 AC XY: 575 AN XY: 74462

African (AFR) AF: 0.0238 AC: 988 AN: 41564

American (AMR) AF: 0.00562 AC: 86 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0179 AC: 62 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000720 AC: 49 AN: 68020

Other (OTH) AF: 0.00993 AC: 21 AN: 2114

Alfa AF: 0.00395 Hom.: 11

Bravo AF: 0.00924

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.0216 AC: 95

ESP6500EA AF: 0.00163 AC: 14

ExAC AF: 0.00338 AC: 411

Asia WGS AF: 0.00318 AC: 11 AN: 3476

EpiCase AF: 0.00115

EpiControl AF: 0.00130

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.8
DANN	Benign	0.51
DEOGEN2	Benign	0.015	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0082	N
LIST_S2	Benign	0.37	T
MetaRNN	Benign	0.0033	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.90	N
PhyloP100		0.081
PrimateAI	Benign	0.17	T
PROVEAN	Benign	0.53	N
REVEL	Benign	0.033
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.078
MVP		0.12
MPC		0.014
ClinPred		0.000026	T
GERP RS		2.7
Varity_R		0.028
gMVP		0.045
Mutation Taster		=100/0	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: rs36020613; hg19: chr11-5536548; COSMIC: COSV66493806; COSMIC: COSV66493806;