chr10-70844506-G-T

Position:

chr10-70844506-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003901.4(SGPL1):c.61G>T(p.Val21Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 1,613,196 control chromosomes in the GnomAD database, including 12,514 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.093 ( 865 hom., cov: 32)

Exomes 𝑓: 0.12 ( 11649 hom. )

Consequence

SGPL1
NM_003901.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.93

Variant links:

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 links:

SGPL1 (HGNC:):

SGPL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014781952).

BP6

Variant 10-70844506-G-T is Benign according to our data. Variant chr10-70844506-G-T is described in ClinVar as [Benign]. Clinvar id is 1232847.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-70844506-G-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SGPL1	NM_003901.4 linkuse as main transcript	c.61G>T	p.Val21Leu	missense_variant	3/15	ENST00000373202.8	NP_003892.2	O95470

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SGPL1	ENST00000373202.8 linkuse as main transcript	c.61G>T	p.Val21Leu	missense_variant	3/15	1	NM_003901.4	ENSP00000362298.3		O95470

Frequencies

GnomAD3 genomes

AF:

0.0935

AC:

14226

AN:

152102

Hom.:

865

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0374

Gnomad AMI

AF:

0.111

Gnomad AMR

AF:

0.0838

Gnomad ASJ

AF:

0.121

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.0259

Gnomad FIN

AF:

0.117

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.136

Gnomad OTH

AF:

0.0967

GnomAD3 exomes

AF:

0.0915

AC:

22995

AN:

251240

Hom.:

1379

AF XY:

0.0909

AC XY:

12342

AN XY:

135778

show subpopulations

Gnomad AFR exome

AF:

0.0366

Gnomad AMR exome

AF:

0.0616

Gnomad ASJ exome

AF:

0.112

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0256

Gnomad FIN exome

AF:

0.118

Gnomad NFE exome

AF:

0.133

Gnomad OTH exome

AF:

0.108

GnomAD4 exome

AF:

0.119

AC:

173719

AN:

1460976

Hom.:

11649

Cov.:

AF XY:

0.116

AC XY:

84637

AN XY:

726846

show subpopulations

Gnomad4 AFR exome

AF:

0.0353

Gnomad4 AMR exome

AF:

0.0655

Gnomad4 ASJ exome

AF:

0.110

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0284

Gnomad4 FIN exome

AF:

0.120

Gnomad4 NFE exome

AF:

0.136

Gnomad4 OTH exome

AF:

0.107

GnomAD4 genome

AF:

0.0934

AC:

14222

AN:

152220

Hom.:

865

Cov.:

AF XY:

0.0893

AC XY:

6648

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.0373

Gnomad4 AMR

AF:

0.0838

Gnomad4 ASJ

AF:

0.121

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.0253

Gnomad4 FIN

AF:

0.117

Gnomad4 NFE

AF:

0.136

Gnomad4 OTH

AF:

0.0956

Alfa

AF:

0.124

Hom.:

2417

Bravo

AF:

0.0894

TwinsUK

AF:

0.154

AC:

572

ALSPAC

AF:

0.148

AC:

571

ESP6500AA

AF:

0.0388

AC:

171

ESP6500EA

AF:

0.138

AC:

1186

ExAC

AF:

0.0918

AC:

11146

Asia WGS

AF:

0.0180

AC:

AN:

3478

EpiCase

AF:

0.133

EpiControl

AF:

0.126

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 05, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Nephrotic syndrome 14

Benign:1

Benign, criteria provided, single submitter

clinical testing

Victorian Clinical Genetics Services, Murdoch Childrens Research Institute

Jun 24, 2022

Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as benign. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with nephrotic syndrome, type 14 (MIM#617575). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from valine to leucine. (I) 0251 - This variant is heterozygous. (I) 0308 - Population frequency for this variant is out of keeping with known incidence of nephrotic syndrome (gnomAD v2: 22998 heterozygotes, 1586 homozygotes). (SB) 0503 - Missense variant consistently predicted to be tolerated by multiple in silico tools or not conserved in placental mammals with a minor amino acid change. (SB) 0604 - Variant is not located in an established domain, motif, hotspot or informative constraint region. (I) 0805 - This variant has strong previous evidence of being benign in unrelated individuals. This variant has been classified multiple times as benign (ClinVar, LOVD). (SB) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.29

T;.

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.058

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.76

T;T

MetaRNN

Benign

0.0015

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

L;.

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.060

N;N

REVEL

Benign

0.052

Sift

Benign

0.43

T;T

Sift4G

Benign

0.65

T;T

Polyphen

0.0

B;.

Vest4

0.064

MutPred

0.10

Loss of ubiquitination at K25 (P = 0.1016);.;

MPC

0.27

ClinPred

0.0057

GERP RS

5.0

Varity_R

0.026

gMVP

0.74

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over