10-70844506-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

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

Publications

20 publications found

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 Gene-Disease associations (from GenCC):

nephrotic syndrome 14
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia

SGPL1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

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 rank	MANE	Protein	UniProt
SGPL1	NM_003901.4 link	c.61G>T	p.Val21Leu	missense_variant	Exon 3 of 15	ENST00000373202.8	NP_003892.2	O95470

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SGPL1	ENST00000373202.8 link	c.61G>T	p.Val21Leu	missense_variant	Exon 3 of 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

GnomAD2 exomes

AF:

0.0915

AC:

22995

AN:

251240

AF XY:

0.0909

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 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

African (AFR)

AF:

0.0353

AC:

1180

AN:

33470

American (AMR)

AF:

0.0655

AC:

2930

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.110

AC:

2886

AN:

26132

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39698

South Asian (SAS)

AF:

0.0284

AC:

2447

AN:

86246

European-Finnish (FIN)

AF:

0.120

AC:

6430

AN:

53380

Middle Eastern (MID)

AF:

0.0862

AC:

497

AN:

5764

European-Non Finnish (NFE)

AF:

0.136

AC:

150913

AN:

1111208

Other (OTH)

AF:

0.107

AC:

6433

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

6751

13502

20254

27005

33756

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0934

AC:

14222

AN:

152220

Hom.:

865

Cov.:

AF XY:

0.0893

AC XY:

6648

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.0373

AC:

1550

AN:

41542

American (AMR)

AF:

0.0838

AC:

1282

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.121

AC:

421

AN:

3466

East Asian (EAS)

AF:

0.000578

AC:

AN:

5188

South Asian (SAS)

AF:

0.0253

AC:

122

AN:

4820

European-Finnish (FIN)

AF:

0.117

AC:

1245

AN:

10602

Middle Eastern (MID)

AF:

0.0918

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.136

AC:

9269

AN:

67988

Other (OTH)

AF:

0.0956

AC:

202

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

651

1302

1953

2604

3255

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.120

Hom.:

3295

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

Dec 05, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nephrotic syndrome 14

Benign:1

Jun 24, 2022

Victorian Clinical Genetics Services, Murdoch Childrens Research Institute

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

(source)

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;.

PhyloP100

1.9

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

PromoterAI

0.0054

Neutral

(source)

Varity_R

0.026

gMVP

0.74

Mutation Taster

=95/5

polymorphism (auto)

(source)

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

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10-70844506-G-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over