chr10-70844610-G-A
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_003901.4(SGPL1):c.165G>A(p.Trp55Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000547 in 1,461,822 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 (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000055 ( 0 hom. )
Consequence
SGPL1
NM_003901.4 stop_gained
NM_003901.4 stop_gained
Scores
4
2
1
Clinical Significance
Conservation
PhyloP100: 5.32
Genes affected
SGPL1 (HGNC:10817): (sphingosine-1-phosphate lyase 1) Enables sphinganine-1-phosphate aldolase activity. Involved in apoptotic signaling pathway; fatty acid metabolic process; and sphingolipid metabolic process. Located in endoplasmic reticulum. Implicated in nephrotic syndrome type 14. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 10-70844610-G-A is Pathogenic according to our data. Variant chr10-70844610-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 2076836.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SGPL1 | NM_003901.4 | c.165G>A | p.Trp55Ter | stop_gained | 3/15 | ENST00000373202.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SGPL1 | ENST00000373202.8 | c.165G>A | p.Trp55Ter | stop_gained | 3/15 | 1 | NM_003901.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461822Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 727210
GnomAD4 exome
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8
AN:
1461822
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Cov.:
31
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AC XY:
5
AN XY:
727210
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ESP6500AA
AF:
AC:
0
ESP6500EA
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1
ExAC
?
AF:
AC:
1
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Feb 11, 2022 | For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with SGPL1-related conditions. This variant is present in population databases (rs370111307, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Trp55*) in the SGPL1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SGPL1 are known to be pathogenic (PMID: 28165339, 28165343). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A
Vest4
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Calibrated prediction
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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