Variant chr1-156041648-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_020131.5(UBQLN4):c.1490G>A(p.Arg497Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000602 in 1,579,030 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000061 ( 0 hom. )

Consequence

UBQLN4
NM_020131.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.68

Variant links:

Genes affected

UBQLN4 (HGNC:1237): (ubiquilin 4) Enables K48-linked polyubiquitin modification-dependent protein binding activity and identical protein binding activity. Involved in cellular response to DNA damage stimulus; negative regulation of double-strand break repair via homologous recombination; and regulation of cellular catabolic process. Located in several cellular components, including autophagosome; nucleoplasm; and site of DNA damage. Part of protein-containing complex. Colocalizes with cytosolic proteasome complex and nuclear proteasome complex. [provided by Alliance of Genome Resources, Apr 2022]

UBQLN4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.13413095).

BS2

High AC in GnomAd4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
UBQLN4	NM_020131.5 linkuse as main transcript	c.1490G>A	p.Arg497Gln	missense_variant	10/11	ENST00000368309.4	NP_064516.2
UBQLN4	NM_001304342.2 linkuse as main transcript	c.1430G>A	p.Arg477Gln	missense_variant	10/11		NP_001291271.1
UBQLN4	XM_024448469.2 linkuse as main transcript	c.1490G>A	p.Arg497Gln	missense_variant	10/11		XP_024304237.1
UBQLN4	XM_047425666.1 linkuse as main transcript	c.956G>A	p.Arg319Gln	missense_variant	10/11		XP_047281622.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBQLN4	ENST00000368309.4 linkuse as main transcript	c.1490G>A	p.Arg497Gln	missense_variant	10/11	1	NM_020131.5	ENSP00000357292	P1	Q9NRR5-1

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152062

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000361

AC:

AN:

193720

Hom.:

AF XY:

0.0000478

AC XY:

AN XY:

104700

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000404

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000108

Gnomad NFE exome

AF:

0.0000463

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000610

AC:

AN:

1426968

Hom.:

Cov.:

AF XY:

0.0000707

AC XY:

AN XY:

707392

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000267

Gnomad4 ASJ exome

AF:

0.000285

Gnomad4 EAS exome

AF:

0.0000259

Gnomad4 SAS exome

AF:

0.000134

Gnomad4 FIN exome

AF:

0.0000575

Gnomad4 NFE exome

AF:

0.0000539

Gnomad4 OTH exome

AF:

0.0000848

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152062

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74262

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000926

Hom.:

Bravo

AF:

0.0000529

ExAC

AF:

0.0000248

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 24, 2024

The c.1490G>A (p.R497Q) alteration is located in exon 10 (coding exon 10) of the UBQLN4 gene. This alteration results from a G to A substitution at nucleotide position 1490, causing the arginine (R) at amino acid position 497 to be replaced by a glutamine (Q). 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

0.064

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0051

Eigen

Benign

-0.030

Eigen_PC

Benign

0.11

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.70

M_CAP

Benign

0.014

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

MutationTaster

Benign

0.99

D;D

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.14

REVEL

Benign

0.085

Sift

Benign

0.62

Sift4G

Benign

0.63

Polyphen

0.87

Vest4

0.14

MVP

0.59

MPC

0.96

ClinPred

0.12

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.098

gMVP

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over