rs544351411
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 6P and 4B. PP3_StrongPP5_ModerateBS2
The NM_018359.5(UFSP2):āc.1373A>Gā(p.Tyr458Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,613,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (ā ).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 33)
Exomes š: 0.000014 ( 0 hom. )
Consequence
UFSP2
NM_018359.5 missense
NM_018359.5 missense
Scores
12
6
1
Clinical Significance
Conservation
PhyloP100: 7.63
Genes affected
UFSP2 (HGNC:25640): (UFM1 specific peptidase 2) This gene encodes a highly conserved cysteine protease. The protein cleaves two C-terminal residues from ubiquitin-fold modifier 1, a ubiquitin-like post-translational modifier protein. Activation of ubiquitin-fold modifier 1 by the encoded protein exposes a C-terminal glycine residue that allows interaction with other proteins and transfer to its target protein. An allelic variant of this gene has been associated with Beukes hip dysplasia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.973
PP5
?
Variant 4-185400429-T-C is Pathogenic according to our data. Variant chr4-185400429-T-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 224821.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-185400429-T-C is described in Lovd as [Likely_pathogenic].
BS2
?
High AC in GnomAdExome4 at 21 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
UFSP2 | NM_018359.5 | c.1373A>G | p.Tyr458Cys | missense_variant | 12/12 | ENST00000264689.11 | |
ANKRD37 | XM_017008176.2 | c.*652T>C | 3_prime_UTR_variant | 4/4 | |||
UFSP2 | NR_028085.2 | n.1444A>G | non_coding_transcript_exon_variant | 12/12 | |||
UFSP2 | NR_144317.2 | n.1572A>G | non_coding_transcript_exon_variant | 12/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
UFSP2 | ENST00000264689.11 | c.1373A>G | p.Tyr458Cys | missense_variant | 12/12 | 2 | NM_018359.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152186Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251190Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135804
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GnomAD4 exome AF: 0.0000144 AC: 21AN: 1461670Hom.: 0 Cov.: 30 AF XY: 0.0000179 AC XY: 13AN XY: 727152
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152186Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74348
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ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Cerebral visual impairment and intellectual disability Pathogenic:1
Likely pathogenic, criteria provided, single submitter | research | Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine | Sep 09, 2015 | This study shows that diverse genetic causes underlie CVI. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
H
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Pathogenic
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MutPred
Loss of ubiquitination at K454 (P = 0.0957);
MVP
MPC
ClinPred
D
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