Genetic Variant NM_145053.5:c.1124G>A (chr11-5515318-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0810

Publications

4 publications found

Variant links:

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]

UBQLNL links:

ENSG00000239920 (HGNC:):

ENSG00000239920 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

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.:

Cov.:

show subpopulations

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

show subpopulations

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.:

Cov.:

AF XY:

0.00156

AC XY:

1135

AN XY:

727240

show subpopulations

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:

AN:

39698

South Asian (SAS)

AF:

0.000209

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.000168

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00641

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000509

AC:

566

AN:

1112006

Other (OTH)

AF:

0.00406

AC:

245

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

155

310

464

619

774

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

192

240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00793

AC:

1208

AN:

152290

Hom.:

Cov.:

AF XY:

0.00772

AC XY:

575

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.0238

AC:

988

AN:

41564

American (AMR)

AF:

0.00562

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0179

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000720

AC:

AN:

68020

Other (OTH)

AF:

0.00993

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

131

197

262

328

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00395

Hom.:

Bravo

AF:

0.00924

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0216

AC:

ESP6500EA

AF:

0.00163

AC:

ExAC

AF:

0.00338

AC:

411

Asia WGS

AF:

0.00318

AC:

AN:

3476

EpiCase

AF:

0.00115

EpiControl

AF:

0.00130

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.78

CADD

Benign

3.8

(source)

DANN

Benign

0.51

DEOGEN2

Benign

0.015

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0082

LIST_S2

Benign

0.37

MetaRNN

Benign

0.0033

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.90

PhyloP100

0.081

PrimateAI

Benign

0.17

PROVEAN

Benign

0.53

REVEL

Benign

0.033

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0010

Vest4

0.078

MVP

0.12

MPC

0.014

ClinPred

0.000026

GERP RS

2.7

Varity_R

0.028

gMVP

0.045

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over