rs865832

chr10-70871869-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_003901.4(SGPL1):c.942C>T(p.Val314=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 1,613,402 control chromosomes in the GnomAD database, including 28,735 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2183 hom., cov: 32)
  • Exomes 𝑓: 0.19 (26552 hom.)
• Consequence: SGPL1 NM_003901.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.160

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]

ACMG classification

Verdict is Benign. Variant got -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 10-70871869-C-T is Benign according to our data. Variant chr10-70871869-C-T is described in ClinVar as [Benign]. Clinvar id is 1242362.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-70871869-C-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.16 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SGPL1	NM_003901.4	c.942C>T	p.Val314=	synonymous_variant	11/15	ENST00000373202.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SGPL1	ENST00000373202.8	c.942C>T	p.Val314=	synonymous_variant	11/15	1	NM_003901.4	P1

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24541 AN: 151826 Hom.: 2187 Cov.: 32

Gnomad AFR AF: 0.0904

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.184

GnomAD3 exomes AF: 0.179 AC: 44856 AN: 251274 Hom.: 4199 AF XY: 0.176 AC XY: 23922 AN XY: 135810

Gnomad AFR exome AF: 0.0904

Gnomad AMR exome AF: 0.197

Gnomad ASJ exome AF: 0.183

Gnomad EAS exome AF: 0.225

Gnomad SAS exome AF: 0.116

Gnomad FIN exome AF: 0.166

Gnomad NFE exome AF: 0.196

Gnomad OTH exome AF: 0.196

GnomAD4 exome AF: 0.188 AC: 274506 AN: 1461458 Hom.: 26552 Cov.: 32 AF XY: 0.186 AC XY: 135222 AN XY: 727052

Gnomad4 AFR exome AF: 0.0898

Gnomad4 AMR exome AF: 0.198

Gnomad4 ASJ exome AF: 0.185

Gnomad4 EAS exome AF: 0.200

Gnomad4 SAS exome AF: 0.121

Gnomad4 FIN exome AF: 0.165

Gnomad4 NFE exome AF: 0.196

Gnomad4 OTH exome AF: 0.187

GnomAD4 genome AF: 0.161 AC: 24533 AN: 151944 Hom.: 2183 Cov.: 32 AF XY: 0.158 AC XY: 11736 AN XY: 74260

Gnomad4 AFR AF: 0.0902

Gnomad4 AMR AF: 0.183

Gnomad4 ASJ AF: 0.194

Gnomad4 EAS AF: 0.217

Gnomad4 SAS AF: 0.119

Gnomad4 FIN AF: 0.163

Gnomad4 NFE AF: 0.196

Gnomad4 OTH AF: 0.183

Alfa AF: 0.191 Hom.: 3749

Bravo AF: 0.166

Asia WGS AF: 0.137 AC: 477 AN: 3478

EpiCase AF: 0.199

EpiControl AF: 0.194

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 05, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
Cadd	Benign	1.5
Dann	Benign	0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs865832; hg19: chr10-72631626; COSMIC: COSV64591461; COSMIC: COSV64591461;