rs761503297
Positions:
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2
The NM_013444.4(UBQLN2):āc.1420C>Gā(p.Pro474Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000504 in 1,210,659 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 24 hemizygotes in GnomAD. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: š 0.000053 ( 0 hom., 2 hem., cov: 24)
Exomes š: 0.000050 ( 0 hom. 22 hem. )
Consequence
UBQLN2
NM_013444.4 missense
NM_013444.4 missense
Scores
1
10
6
Clinical Significance
Conservation
PhyloP100: 7.36
Genes affected
UBQLN2 (HGNC:12509): (ubiquilin 2) This gene encodes an ubiquitin-like protein (ubiquilin) that shares high degree of similarity with related products in yeast, rat and frog. Ubiquilins contain a N-terminal ubiquitin-like domain and a C-terminal ubiquitin-associated domain. They physically associate with both proteasomes and ubiquitin ligases; and thus, are thought to functionally link the ubiquitination machinery to the proteasome to affect in vivo protein degradation. This ubiquilin has also been shown to bind the ATPase domain of the Hsp70-like Stch protein. [provided by RefSeq, Oct 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP6
Variant X-56565293-C-G is Benign according to our data. Variant chrX-56565293-C-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 448847.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}. Variant chrX-56565293-C-G is described in Lovd as [Likely_benign].
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0000532 (6/112707) while in subpopulation NFE AF= 0.0000939 (5/53242). AF 95% confidence interval is 0.0000369. There are 0 homozygotes in gnomad4. There are 2 alleles in male gnomad4 subpopulation. Median coverage is 24. This position pass quality control queck.
BS2
High Hemizygotes in GnomAd4 at 2 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
UBQLN2 | NM_013444.4 | c.1420C>G | p.Pro474Ala | missense_variant | 1/1 | ENST00000338222.7 | NP_038472.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
UBQLN2 | ENST00000338222.7 | c.1420C>G | p.Pro474Ala | missense_variant | 1/1 | NM_013444.4 | ENSP00000345195 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000532 AC: 6AN: 112707Hom.: 0 Cov.: 24 AF XY: 0.0000574 AC XY: 2AN XY: 34861
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000110 AC: 2AN: 182330Hom.: 0 AF XY: 0.0000150 AC XY: 1AN XY: 66882
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GnomAD4 exome AF: 0.0000501 AC: 55AN: 1097952Hom.: 0 Cov.: 31 AF XY: 0.0000606 AC XY: 22AN XY: 363310
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GnomAD4 genome AF: 0.0000532 AC: 6AN: 112707Hom.: 0 Cov.: 24 AF XY: 0.0000574 AC XY: 2AN XY: 34861
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Nov 20, 2017 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 21, 2018 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Mar 08, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
T
MetaSVM
Uncertain
D
MutationAssessor
Benign
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Benign
T
Sift4G
Benign
T
Polyphen
P
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at