rs10509327

Variant names:

• chr10-70834406-G-T
• rs10509327
• NM_003901.4:c.28-10067G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003901.4(SGPL1):​c.28-10067G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,208 control chromosomes in the GnomAD database, including 1,325 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.12 (1325 hom., cov: 32)
• Consequence: SGPL1 NM_003901.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.529
• Publications: 5 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 14

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGPL1	NM_003901.4	c.28-10067G>T		intron_variant	Intron 2 of 14	ENST00000373202.8	NP_003892.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SGPL1	ENST00000373202.8	c.28-10067G>T		intron_variant	Intron 2 of 14	1	NM_003901.4	ENSP00000362298.3

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18080 AN: 152090 Hom.: 1325 Cov.: 32

Gnomad AFR AF: 0.0419

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.0868

Gnomad SAS AF: 0.0857

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.123

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.119 AC: 18071 AN: 152208 Hom.: 1325 Cov.: 32 AF XY: 0.115 AC XY: 8541 AN XY: 74418

African (AFR) AF: 0.0418 AC: 1736 AN: 41546

American (AMR) AF: 0.105 AC: 1600 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 555 AN: 3472

East Asian (EAS) AF: 0.0862 AC: 447 AN: 5184

South Asian (SAS) AF: 0.0847 AC: 409 AN: 4826

European-Finnish (FIN) AF: 0.149 AC: 1576 AN: 10582

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.167 AC: 11356 AN: 67982

Other (OTH) AF: 0.123 AC: 259 AN: 2114

Alfa AF: 0.152 Hom.: 3115

Bravo AF: 0.113

Asia WGS AF: 0.0770 AC: 269 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.4
DANN	Benign	0.69
PhyloP100		0.53
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10509327; hg19: chr10-72594162;