chr1-156051139-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020131.5(UBQLN4):​c.449G>A​(p.Gly150Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,574 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

UBQLN4
NM_020131.5 missense

Scores

7
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.28
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
UBQLN4NM_020131.5 linkuse as main transcriptc.449G>A p.Gly150Glu missense_variant 3/11 ENST00000368309.4 NP_064516.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
UBQLN4ENST00000368309.4 linkuse as main transcriptc.449G>A p.Gly150Glu missense_variant 3/111 NM_020131.5 ENSP00000357292 P1Q9NRR5-1
UBQLN4ENST00000472638.1 linkuse as main transcriptn.398G>A non_coding_transcript_exon_variant 3/55

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1460574
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
726574
show subpopulations
Gnomad4 AFR exome
AF:
0.0000598
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

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 submitterclinical testingAmbry GeneticsMay 01, 2024The c.449G>A (p.G150E) alteration is located in exon 3 (coding exon 3) of the UBQLN4 gene. This alteration results from a G to A substitution at nucleotide position 449, causing the glycine (G) at amino acid position 150 to be replaced by a glutamic acid (E). 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
0.12
BayesDel_addAF
Uncertain
0.065
T
BayesDel_noAF
Benign
-0.14
CADD
Benign
23
DANN
Benign
0.96
DEOGEN2
Benign
0.023
T
Eigen
Benign
0.037
Eigen_PC
Benign
0.0091
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.74
T
M_CAP
Uncertain
0.089
D
MetaRNN
Uncertain
0.63
D
MetaSVM
Benign
-0.40
T
MutationAssessor
Benign
1.5
L
MutationTaster
Benign
0.98
D;D
PrimateAI
Uncertain
0.65
T
PROVEAN
Benign
-0.76
N
REVEL
Uncertain
0.38
Sift
Benign
0.062
T
Sift4G
Uncertain
0.010
D
Polyphen
1.0
D
Vest4
0.69
MutPred
0.28
Gain of solvent accessibility (P = 0.024);
MVP
0.67
MPC
0.85
ClinPred
0.42
T
GERP RS
2.5
Varity_R
0.069
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.

Other links and lift over

hg19: chr1-156020930; API