rs761503297

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2

The NM_013444.4(UBQLN2):ā€‹c.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

Scores

1
10
6

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 7.36
Variant links:
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]

Genome browser will be placed here

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
UBQLN2NM_013444.4 linkuse as main transcriptc.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
UBQLN2ENST00000338222.7 linkuse as main transcriptc.1420C>G p.Pro474Ala missense_variant 1/1 NM_013444.4 ENSP00000345195 P1

Frequencies

GnomAD3 genomes
AF:
0.0000532
AC:
6
AN:
112707
Hom.:
0
Cov.:
24
AF XY:
0.0000574
AC XY:
2
AN XY:
34861
show subpopulations
Gnomad AFR
AF:
0.0000322
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000939
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000110
AC:
2
AN:
182330
Hom.:
0
AF XY:
0.0000150
AC XY:
1
AN XY:
66882
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
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:
0.0000246
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000501
AC:
55
AN:
1097952
Hom.:
0
Cov.:
31
AF XY:
0.0000606
AC XY:
22
AN XY:
363310
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:
0.0000629
Gnomad4 OTH exome
AF:
0.0000434
GnomAD4 genome
AF:
0.0000532
AC:
6
AN:
112707
Hom.:
0
Cov.:
24
AF XY:
0.0000574
AC XY:
2
AN XY:
34861
show subpopulations
Gnomad4 AFR
AF:
0.0000322
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000939
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000142
Hom.:
1
Bravo
AF:
0.0000189
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.000346
AC:
1
ExAC
AF:
0.0000247
AC:
3

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 submitterclinical testingEurofins Ntd Llc (ga)Nov 20, 2017- -
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpSep 21, 2018- -
not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAthena DiagnosticsMar 08, 2017- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.43
BayesDel_addAF
Uncertain
0.091
D
BayesDel_noAF
Uncertain
-0.060
CADD
Benign
22
DANN
Benign
0.82
DEOGEN2
Benign
0.22
T
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.97
D
M_CAP
Pathogenic
0.32
D
MetaRNN
Uncertain
0.46
T
MetaSVM
Uncertain
0.33
D
MutationAssessor
Benign
2.0
M
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.75
T
PROVEAN
Uncertain
-3.3
D
REVEL
Uncertain
0.64
Sift
Benign
0.71
T
Sift4G
Benign
0.28
T
Polyphen
0.88
P
Vest4
0.40
MVP
0.85
MPC
0.81
ClinPred
0.21
T
GERP RS
4.8
Varity_R
0.31
gMVP
0.83

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs761503297; hg19: chrX-56591726; API