rs768910794

chrX-56564452-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_013444.4(UBQLN2):c.579C>T(p.Ser193=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000038 in 1,209,561 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 12 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000054 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 0.000036 (0 hom. 12 hem.)
• Consequence: UBQLN2 NM_013444.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.23

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant X-56564452-C-T is Benign according to our data. Variant chrX-56564452-C-T is described in ClinVar as [Benign]. Clinvar id is 586918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.23 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0000538 (6/111587) while in subpopulation AMR AF= 0.000473 (5/10580). AF 95% confidence interval is 0.000186. There are 0 homozygotes in gnomad4. There are 0 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
• BS2: High Hemizygotes in GnomAdExome at 10 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UBQLN2	NM_013444.4	c.579C>T	p.Ser193=	synonymous_variant	1/1	ENST00000338222.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBQLN2	ENST00000338222.7	c.579C>T	p.Ser193=	synonymous_variant	1/1		NM_013444.4	P1

Frequencies

GnomAD3 genomes AF: 0.0000538 AC: 6 AN: 111587 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 33767

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000473

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000665

GnomAD3 exomes AF: 0.000186 AC: 34 AN: 183077 Hom.: 0 AF XY: 0.000148 AC XY: 10 AN XY: 67573

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00117

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000442

GnomAD4 exome AF: 0.0000364 AC: 40 AN: 1097974 Hom.: 0 Cov.: 31 AF XY: 0.0000330 AC XY: 12 AN XY: 363336

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000966

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: 0.00000119

Gnomad4 OTH exome AF: 0.0000868

GnomAD4 genome AF: 0.0000538 AC: 6 AN: 111587 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 33767

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000473

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000665

Alfa AF: 0.000498 Hom.: 3

Bravo AF: 0.000110

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Sep 17, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Feb 28, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
Cadd	Benign	13
Dann	Benign	0.91
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

Other links and lift over

dbSNP: rs768910794; hg19: chrX-56590885; COSMIC: COSV57740866;