X-56564116-A-G
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2
The NM_013444.4(UBQLN2):āc.243A>Gā(p.Leu81=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000331 in 1,209,739 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: š 0.000018 ( 0 hom., 2 hem., cov: 23)
Exomes š: 0.0000018 ( 0 hom. 1 hem. )
Consequence
UBQLN2
NM_013444.4 synonymous
NM_013444.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.30
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 -10 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.58).
BP6
Variant X-56564116-A-G is Benign according to our data. Variant chrX-56564116-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 368607.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.
BP7
Synonymous conserved (PhyloP=1.3 with no splicing effect.
BS2
High Hemizygotes in GnomAd4 at 2 XL gene
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
|---|---|---|---|---|---|---|---|
| UBQLN2 | NM_013444.4 | c.243A>G | p.Leu81= | synonymous_variant | 1/1 | ENST00000338222.7 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| UBQLN2 | ENST00000338222.7 | c.243A>G | p.Leu81= | synonymous_variant | 1/1 | NM_013444.4 | P1 |
Frequencies
GnomAD3 genomes 0.0000178 AC: 2AN: 112337Hom.: 0 Cov.: 23 AF XY: 0.0000580 AC XY: 2AN XY: 34499
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GnomAD3 exomes AF: 0.0000110 AC: 2AN: 181655Hom.: 0 AF XY: 0.0000151 AC XY: 1AN XY: 66405
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GnomAD4 exome AF: 0.00000182 AC: 2AN: 1097348Hom.: 0 Cov.: 30 AF XY: 0.00000276 AC XY: 1AN XY: 362716
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GnomAD4 genome 0.0000178 AC: 2AN: 112391Hom.: 0 Cov.: 23 AF XY: 0.0000579 AC XY: 2AN XY: 34563
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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
Amyotrophic lateral sclerosis type 15 Uncertain:1Benign:1
| Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jun 05, 2021 | - - |
| Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Amyotrophic Lateral Sclerosis, Dominant Benign:1
| Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at