chr10-70877258-GTCT-G
Variant summary
Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PM4_SupportingPP5
The NM_001438353.1(SGPL1):c.1668_1670delCTT(p.Phe556del) variant causes a disruptive inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,718 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
SGPL1
NM_001438353.1 disruptive_inframe_deletion
NM_001438353.1 disruptive_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.64
Publications
10 publications found
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]
SGPL1 Gene-Disease associations (from GenCC):
- nephrotic syndrome 14Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_001438353.1. Strenght limited to Supporting due to length of the change: 1aa.
PP5
Variant 10-70877258-GTCT-G is Pathogenic according to our data. Variant chr10-70877258-GTCT-G is described in ClinVar as Pathogenic. ClinVar VariationId is 430862.Status of the report is no_assertion_criteria_provided, 0 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001438353.1. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| SGPL1 | NM_003901.4 | MANE Select | c.1635_1637delCTT | p.Phe545del | disruptive_inframe_deletion | Exon 15 of 15 | NP_003892.2 | ||
| SGPL1 | NM_001438353.1 | c.1668_1670delCTT | p.Phe556del | disruptive_inframe_deletion | Exon 16 of 16 | NP_001425282.1 | |||
| SGPL1 | NM_001438354.1 | c.1635_1637delCTT | p.Phe545del | disruptive_inframe_deletion | Exon 15 of 15 | NP_001425283.1 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| SGPL1 | ENST00000373202.8 | TSL:1 MANE Select | c.1635_1637delCTT | p.Phe545del | disruptive_inframe_deletion | Exon 15 of 15 | ENSP00000362298.3 | ||
| SGPL1 | ENST00000697928.1 | c.1635_1637delCTT | p.Phe545del | disruptive_inframe_deletion | Exon 15 of 15 | ENSP00000513482.1 | |||
| SGPL1 | ENST00000697931.1 | c.1635_1637delCTT | p.Phe545del | disruptive_inframe_deletion | Exon 15 of 15 | ENSP00000513485.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD2 exomes AF: 0.00000398 AC: 1AN: 251468 AF XY: 0.00000736 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
251468
AF XY:
Gnomad AFR exome
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Gnomad ASJ exome
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Gnomad FIN exome
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Gnomad NFE exome
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Gnomad OTH exome
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GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461718Hom.: 0 AF XY: 0.00000138 AC XY: 1AN XY: 727180 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1461718
Hom.:
AF XY:
AC XY:
1
AN XY:
727180
show subpopulations
African (AFR)
AF:
AC:
1
AN:
33478
American (AMR)
AF:
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26134
East Asian (EAS)
AF:
AC:
0
AN:
39698
South Asian (SAS)
AF:
AC:
0
AN:
86252
European-Finnish (FIN)
AF:
AC:
0
AN:
53420
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1111850
Other (OTH)
AF:
AC:
0
AN:
60394
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
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0.95
Allele balance
Age Distribution
Exome Het
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GnomAD4 genome
GnomAD4 genome
Cov.:
32
Alfa
AF:
Hom.:
ClinVar
ClinVar submissions as Germline
View on ClinVar Significance:Pathogenic
Revision:no assertion criteria provided
Pathogenic
VUS
Benign
Condition
1
-
-
Nephrotic syndrome 14 (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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