Variant 1-156041545-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_020131.5(UBQLN4):c.1593C>T(p.Ser531=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00785 in 1,612,624 control chromosomes in the GnomAD database, including 61 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0059 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0081 ( 59 hom. )

Consequence

UBQLN4
NM_020131.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.129

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 1-156041545-G-A is Benign according to our data. Variant chr1-156041545-G-A is described in ClinVar as [Benign]. Clinvar id is 781585.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.129 with no splicing effect.

BS2

High AC in GnomAd4 at 898 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
UBQLN4	NM_020131.5 linkuse as main transcript	c.1593C>T	p.Ser531=	synonymous_variant	10/11	ENST00000368309.4
UBQLN4	NM_001304342.2 linkuse as main transcript	c.1533C>T	p.Ser511=	synonymous_variant	10/11
UBQLN4	XM_024448469.2 linkuse as main transcript	c.1593C>T	p.Ser531=	synonymous_variant	10/11
UBQLN4	XM_047425666.1 linkuse as main transcript	c.1059C>T	p.Ser353=	synonymous_variant	10/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBQLN4	ENST00000368309.4 linkuse as main transcript	c.1593C>T	p.Ser531=	synonymous_variant	10/11	1	NM_020131.5	P1	Q9NRR5-1

Frequencies

GnomAD3 genomes

AF:

0.00590

AC:

898

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00116

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00563

Gnomad ASJ

AF:

0.00230

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.0117

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00905

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00631

AC:

1580

AN:

250384

Hom.:

AF XY:

0.00641

AC XY:

867

AN XY:

135316

show subpopulations

Gnomad AFR exome

AF:

0.000987

Gnomad AMR exome

AF:

0.00352

Gnomad ASJ exome

AF:

0.00269

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00164

Gnomad FIN exome

AF:

0.0125

Gnomad NFE exome

AF:

0.00931

Gnomad OTH exome

AF:

0.00673

GnomAD4 exome

AF:

0.00806

AC:

11763

AN:

1460298

Hom.:

Cov.:

AF XY:

0.00783

AC XY:

5686

AN XY:

726488

show subpopulations

Gnomad4 AFR exome

AF:

0.00111

Gnomad4 AMR exome

AF:

0.00385

Gnomad4 ASJ exome

AF:

0.00307

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00151

Gnomad4 FIN exome

AF:

0.0112

Gnomad4 NFE exome

AF:

0.00925

Gnomad4 OTH exome

AF:

0.00755

GnomAD4 genome

AF:

0.00590

AC:

898

AN:

152326

Hom.:

Cov.:

AF XY:

0.00556

AC XY:

414

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00115

Gnomad4 AMR

AF:

0.00562

Gnomad4 ASJ

AF:

0.00230

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.0117

Gnomad4 NFE

AF:

0.00905

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00786

Hom.:

Bravo

AF:

0.00572

EpiCase

AF:

0.00770

EpiControl

AF:

0.00623

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 28, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

7.5

DANN

Benign

0.68

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

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

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