Variant 1-156041596-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_020131.5(UBQLN4):c.1542C>T(p.Pro514=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00405 in 1,612,290 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0025 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0042 ( 19 hom. )

Consequence

UBQLN4
NM_020131.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.802

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 1-156041596-G-A is Benign according to our data. Variant chr1-156041596-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2639445.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.802 with no splicing effect.

BS2

High AC in GnomAd4 at 385 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
UBQLN4	NM_020131.5 linkuse as main transcript	c.1542C>T	p.Pro514=	synonymous_variant	10/11	ENST00000368309.4	NP_064516.2
UBQLN4	NM_001304342.2 linkuse as main transcript	c.1482C>T	p.Pro494=	synonymous_variant	10/11		NP_001291271.1
UBQLN4	XM_024448469.2 linkuse as main transcript	c.1542C>T	p.Pro514=	synonymous_variant	10/11		XP_024304237.1
UBQLN4	XM_047425666.1 linkuse as main transcript	c.1008C>T	p.Pro336=	synonymous_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.1542C>T	p.Pro514=	synonymous_variant	10/11	1	NM_020131.5	ENSP00000357292	P1	Q9NRR5-1

Frequencies

GnomAD3 genomes

AF:

0.00252

AC:

384

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000796

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00621

Gnomad FIN

AF:

0.00574

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00362

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00294

AC:

726

AN:

246818

Hom.:

AF XY:

0.00328

AC XY:

438

AN XY:

133476

show subpopulations

Gnomad AFR exome

AF:

0.000314

Gnomad AMR exome

AF:

0.000677

Gnomad ASJ exome

AF:

0.000101

Gnomad EAS exome

AF:

0.000165

Gnomad SAS exome

AF:

0.00680

Gnomad FIN exome

AF:

0.00533

Gnomad NFE exome

AF:

0.00318

Gnomad OTH exome

AF:

0.00367

GnomAD4 exome

AF:

0.00421

AC:

6143

AN:

1459958

Hom.:

Cov.:

AF XY:

0.00431

AC XY:

3131

AN XY:

726238

show subpopulations

Gnomad4 AFR exome

AF:

0.000449

Gnomad4 AMR exome

AF:

0.000675

Gnomad4 ASJ exome

AF:

0.000230

Gnomad4 EAS exome

AF:

0.0000758

Gnomad4 SAS exome

AF:

0.00674

Gnomad4 FIN exome

AF:

0.00510

Gnomad4 NFE exome

AF:

0.00451

Gnomad4 OTH exome

AF:

0.00353

GnomAD4 genome

AF:

0.00253

AC:

385

AN:

152332

Hom.:

Cov.:

AF XY:

0.00259

AC XY:

193

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.000794

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00642

Gnomad4 FIN

AF:

0.00574

Gnomad4 NFE

AF:

0.00362

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.00305

Hom.:

Bravo

AF:

0.00193

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2022

UBQLN4: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

7.6

DANN

Uncertain

0.98

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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