NM_003901.4:c.28-10037A>G

Variant names:

• chr10-70834436-A-G
• rs1767174
• NM_003901.4:c.28-10037A>G

Variant summary

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

The NM_003901.4(SGPL1):​c.28-10037A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,230 control chromosomes in the GnomAD database, including 2,131 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 0.16 (2131 hom., cov: 32)
• Consequence: SGPL1 NM_003901.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.406
• Publications: 0 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: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, ClinGen, PanelApp Australia, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003901.4. 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.28-10037A>G		intron	N/A	NP_003892.2
	SGPL1	NM_001438353.1		c.28-10037A>G		intron	N/A	NP_001425282.1
	SGPL1	NM_001438354.1		c.28-10037A>G		intron	N/A	NP_001425283.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGPL1	ENST00000373202.8	TSL:1 MANE Select	c.28-10037A>G		intron	N/A	ENSP00000362298.3	O95470
	SGPL1	ENST00000697928.1		c.28-10037A>G		intron	N/A	ENSP00000513482.1	O95470
	SGPL1	ENST00000697931.1		c.28-10037A>G		intron	N/A	ENSP00000513485.1	O95470

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24001 AN: 152112 Hom.: 2135 Cov.: 32

Gnomad AFR AF: 0.0744

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.0816

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.183

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

GnomAD4 genome AF: 0.158 AC: 23996 AN: 152230 Hom.: 2131 Cov.: 32 AF XY: 0.158 AC XY: 11729 AN XY: 74420

African (AFR) AF: 0.0743 AC: 3087 AN: 41564

American (AMR) AF: 0.187 AC: 2865 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.146 AC: 508 AN: 3470

East Asian (EAS) AF: 0.131 AC: 677 AN: 5170

South Asian (SAS) AF: 0.0821 AC: 396 AN: 4826

European-Finnish (FIN) AF: 0.234 AC: 2472 AN: 10584

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.196 AC: 13348 AN: 67990

Other (OTH) AF: 0.181 AC: 383 AN: 2112

Alfa AF: 0.174 Hom.: 280

Bravo AF: 0.157

Asia WGS AF: 0.0840 AC: 291 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.5
DANN	Benign	0.79
PhyloP100		0.41
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: rs1767174; hg19: chr10-72594192;