rs121908317
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Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_StrongPP5_Moderate
The NM_020427.3(SLURP1):c.286C>T(p.Arg96Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,607,922 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 Pathogenic (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000016 ( 0 hom. )
Consequence
SLURP1
NM_020427.3 stop_gained
NM_020427.3 stop_gained
Scores
2
2
3
Clinical Significance
Conservation
PhyloP100: 0.245
Genes affected
SLURP1 (HGNC:18746): (secreted LY6/PLAUR domain containing 1) The protein encoded by this gene is a member of the Ly6/uPAR family but lacks a GPI-anchoring signal sequence. It is thought that this secreted protein contains antitumor activity. Mutations in this gene have been associated with Mal de Meleda, a rare autosomal recessive skin disorder. This gene maps to the same chromosomal region as several members of the Ly6/uPAR family of glycoprotein receptors. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 5 pathogenic variants in the truncated region.
PP5
?
Variant 8-142741169-G-A is Pathogenic according to our data. Variant chr8-142741169-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 4601.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-142741169-G-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLURP1 | NM_020427.3 | c.286C>T | p.Arg96Ter | stop_gained | 3/3 | ENST00000246515.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLURP1 | ENST00000246515.2 | c.286C>T | p.Arg96Ter | stop_gained | 3/3 | 1 | NM_020427.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152080Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000122 AC: 3AN: 245352Hom.: 0 AF XY: 0.0000150 AC XY: 2AN XY: 133488
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GnomAD4 exome AF: 0.0000158 AC: 23AN: 1455724Hom.: 0 Cov.: 31 AF XY: 0.0000207 AC XY: 15AN XY: 724342
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152198Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74416
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Acroerythrokeratoderma Pathogenic:2
Pathogenic, no assertion criteria provided | literature only | OMIM | Apr 01, 2001 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Neuberg Centre For Genomic Medicine, NCGM | Feb 14, 2023 | The stop gain c.286C>T (p.Arg96Ter) variant in SLURP1 gene has been reported in homozygous state in indidviduals affected with Meleda disease (Harjama L et al. 2020; Akbar A et al. 2019; Wajid M et al. 2009). The p.Arg96Ter variant has allele frequency 0.001% in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. This variant has been reported to the ClinVar database as Pathogenic (multiple submiters). The nucleotide change c.286C>T in SLURP1 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants have been previously reported to be disease causing. For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Benign
N
MutationTaster
Benign
A
Vest4
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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