rs538017286
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 8P and 5B. PVS1BP6BS2
The NM_001412844.1(SULF1):c.3G>A(p.Met1?) variant causes a start lost change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000385 in 1,610,964 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000038 ( 0 hom. )
Consequence
SULF1
NM_001412844.1 start_lost
NM_001412844.1 start_lost
Scores
11
6
2
Clinical Significance
Conservation
PhyloP100: 10.0
Genes affected
SULF1 (HGNC:20391): (sulfatase 1) This gene encodes an extracellular heparan sulfate endosulfatase. The encoded enzyme selectively removes 6-O-sulfate groups from heparan sulfate chains of heparan sulfate proteoglycans (HSPGs). The enzyme is secreted through the Golgi and is subsequently localized to the cell surface. The expression of this gene may be down-regulated in several types of cancer, including hepatocellular (HCC), ovarian and breast cancers. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PVS1
Start lost variant, no new inframe start found.
BP6
Variant 8-69586473-G-A is Benign according to our data. Variant chr8-69586473-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 221945.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
BS2
High AC in GnomAd4 at 7 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SULF1 | NM_001128205.2 | c.529G>A | p.Gly177Ser | missense_variant | 7/23 | ENST00000402687.9 | NP_001121677.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SULF1 | ENST00000402687.9 | c.529G>A | p.Gly177Ser | missense_variant | 7/23 | 1 | NM_001128205.2 | ENSP00000385704.4 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152066Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000202 AC: 5AN: 247934Hom.: 0 AF XY: 0.0000298 AC XY: 4AN XY: 134128
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GnomAD4 exome AF: 0.0000377 AC: 55AN: 1458780Hom.: 0 Cov.: 31 AF XY: 0.0000441 AC XY: 32AN XY: 725676
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GnomAD4 genome AF: 0.0000460 AC: 7AN: 152184Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74386
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 28, 2023 | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 177 of the SULF1 protein (p.Gly177Ser). This variant is present in population databases (rs538017286, gnomAD 0.005%). This missense change has been observed in individual(s) with ocular developmental anomalies (PMID: 26893459). ClinVar contains an entry for this variant (Variation ID: 221945). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. - |
Anophthalmia-microphthalmia syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Paul Sabatier University EA-4555, Paul Sabatier University | Jan 01, 2013 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
D;D;D;D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;.;.;.
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Uncertain
M;M;M;M
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D;D
REVEL
Pathogenic
Sift
Uncertain
D;D;D;D
Sift4G
Uncertain
D;D;D;D
Polyphen
P;P;P;P
Vest4
MutPred
Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);
MVP
MPC
ClinPred
D
GERP RS
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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