rs12770335

Variant names:

Your query was ambiguous. Multiple possible variants found:

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:5

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: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, ClinGen, PanelApp Australia, Labcorp Genetics (formerly Invitae)

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 VariationId 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.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SGPL1	NM_003901.4	MANE Select	c.61G>T	p.Val21Leu	missense	Exon 3 of 15	NP_003892.2
SGPL1	NM_001438353.1		c.61G>T	p.Val21Leu	missense	Exon 3 of 16	NP_001425282.1
SGPL1	NM_001438354.1		c.61G>T	p.Val21Leu	missense	Exon 3 of 15	NP_001425283.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SGPL1	ENST00000373202.8	TSL:1 MANE Select	c.61G>T	p.Val21Leu	missense	Exon 3 of 15	ENSP00000362298.3	O95470
SGPL1	ENST00000697928.1		c.61G>T	p.Val21Leu	missense	Exon 3 of 15	ENSP00000513482.1	O95470
SGPL1	ENST00000697931.1		c.61G>T	p.Val21Leu	missense	Exon 3 of 15	ENSP00000513485.1	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

Age Distribution

Exome Het

Exome Hom

Variant carriers

5198

10396

15594

20792

25990

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

Age Distribution

Genome Het

Genome Hom

Variant carriers

156

312

468

624

780

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Nephrotic syndrome 14 (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

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

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.058

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.76

MetaRNN

Benign

0.0015

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

PhyloP100

1.9

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.060

REVEL

Benign

0.052

Sift

Benign

0.43

Sift4G

Benign

0.65

Polyphen

0.0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over