rs137852844
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1PM2PM5PP3
The ENST00000272902.10(SUMF1):c.1076C>T(p.Ser359Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000335 in 1,614,076 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S359W) has been classified as Likely pathogenic.
Frequency
Consequence
ENST00000272902.10 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SUMF1 | NM_182760.4 | c.1076C>T | p.Ser359Leu | missense_variant | 9/9 | ENST00000272902.10 | NP_877437.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SUMF1 | ENST00000272902.10 | c.1076C>T | p.Ser359Leu | missense_variant | 9/9 | 1 | NM_182760.4 | ENSP00000272902 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152214Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000321 AC: 8AN: 249110Hom.: 0 AF XY: 0.0000371 AC XY: 5AN XY: 134844
GnomAD4 exome AF: 0.0000342 AC: 50AN: 1461862Hom.: 0 Cov.: 33 AF XY: 0.0000316 AC XY: 23AN XY: 727234
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152214Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74358
ClinVar
Submissions by phenotype
Multiple sulfatase deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jul 27, 2022 | This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 359 of the SUMF1 protein (p.Ser359Leu). This variant is present in population databases (rs137852844, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with SUMF1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1418935). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at