rs865832

Variant names:

• chr10-70871869-C-T
• rs865832
• NM_003901.4:c.942C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_003901.4(SGPL1):​c.942C>T​(p.Val314Val) 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:3
• Conservation: PhyloP100: -0.160
• Publications: 23 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 -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 VariationId is 1242362.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.

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.942C>T	p.Val314Val	synonymous	Exon 11 of 15	NP_003892.2
	SGPL1	NM_001438353.1		c.975C>T	p.Val325Val	synonymous	Exon 12 of 16	NP_001425282.1
	SGPL1	NM_001438354.1		c.942C>T	p.Val314Val	synonymous	Exon 11 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.942C>T	p.Val314Val	synonymous	Exon 11 of 15	ENSP00000362298.3	O95470
	SGPL1	ENST00000697928.1		c.942C>T	p.Val314Val	synonymous	Exon 11 of 15	ENSP00000513482.1	O95470
	SGPL1	ENST00000697931.1		c.942C>T	p.Val314Val	synonymous	Exon 11 of 15	ENSP00000513485.1	O95470

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

GnomAD2 exomes AF: 0.179 AC: 44856 AN: 251274 AF XY: 0.176

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 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

African (AFR) AF: 0.0898 AC: 3007 AN: 33470

American (AMR) AF: 0.198 AC: 8830 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 4831 AN: 26128

East Asian (EAS) AF: 0.200 AC: 7947 AN: 39698

South Asian (SAS) AF: 0.121 AC: 10432 AN: 86206

European-Finnish (FIN) AF: 0.165 AC: 8815 AN: 53420

Middle Eastern (MID) AF: 0.213 AC: 1227 AN: 5754

European-Non Finnish (NFE) AF: 0.196 AC: 218123 AN: 1111710

Other (OTH) AF: 0.187 AC: 11294 AN: 60374

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

African (AFR) AF: 0.0902 AC: 3736 AN: 41432

American (AMR) AF: 0.183 AC: 2787 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 672 AN: 3468

East Asian (EAS) AF: 0.217 AC: 1118 AN: 5152

South Asian (SAS) AF: 0.119 AC: 571 AN: 4810

European-Finnish (FIN) AF: 0.163 AC: 1721 AN: 10552

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.196 AC: 13340 AN: 67950

Other (OTH) AF: 0.183 AC: 386 AN: 2110

Alfa AF: 0.188 Hom.: 4525

Bravo AF: 0.166

Asia WGS AF: 0.137 AC: 477 AN: 3478

EpiCase AF: 0.199

EpiControl AF: 0.194

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	1.5
DANN	Benign	0.60
PhyloP100		-0.16
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=90/10	polymorphism (auto)

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

Other links and lift over

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