Variant chr1-156051210-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020131.5(UBQLN4):c.378T>G(p.Ser126Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,684 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: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

UBQLN4
NM_020131.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0950

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10675079).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBQLN4	NM_020131.5 linkuse as main transcript	c.378T>G	p.Ser126Arg	missense_variant	3/11	ENST00000368309.4	NP_064516.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBQLN4	ENST00000368309.4 linkuse as main transcript	c.378T>G	p.Ser126Arg	missense_variant	3/11	1	NM_020131.5	ENSP00000357292	P1	Q9NRR5-1
UBQLN4	ENST00000472638.1 linkuse as main transcript	n.327T>G		non_coding_transcript_exon_variant	3/5	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1458684

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725316

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Apr 09, 2024

The c.378T>G (p.S126R) alteration is located in exon 3 (coding exon 3) of the UBQLN4 gene. This alteration results from a T to G substitution at nucleotide position 378, causing the serine (S) at amino acid position 126 to be replaced by an arginine (R). 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

Uncertain

0.36

BayesDel_addAF

Benign

0.0035

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.022

Eigen

Benign

-0.98

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.82

M_CAP

Benign

0.064

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.5

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.2

REVEL

Benign

0.23

Sift

Benign

0.13

Sift4G

Benign

0.22

Polyphen

0.079

Vest4

0.46

MutPred

0.31

Loss of phosphorylation at S126 (P = 0.004);

MVP

0.53

MPC

0.74

ClinPred

0.16

GERP RS

0.36

Varity_R

0.089

gMVP

0.61

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over