Genetic Variant NM_152386.4:c.136C>A (chr2-222424738-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152386.4(SGPP2):c.136C>A(p.Pro46Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000783 in 1,277,952 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P46S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.8e-7 ( 0 hom. )

Consequence

SGPP2
NM_152386.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0590

Publications

0 publications found

Variant links:

Genes affected

SGPP2 (HGNC:19953): (sphingosine-1-phosphate phosphatase 2) The protein encoded by this gene is a transmembrane protein that degrades the bioactive signaling molecule sphingosine 1-phosphate. The encoded protein is induced during inflammatory responses and has been shown to be downregulated by the microRNA-31 tumor suppressor. Alternative splice variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2016]

SGPP2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14550143).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152386.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SGPP2	NM_152386.4	MANE Select	c.136C>A	p.Pro46Thr	missense	Exon 1 of 5	NP_689599.2
SGPP2	NM_001320833.2		c.-392C>A		5_prime_UTR	Exon 1 of 6	NP_001307762.1	Q8IWX5-2
SGPP2	NM_001320834.2		c.-166+660C>A		intron	N/A	NP_001307763.1	Q8IWX5-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SGPP2	ENST00000321276.8	TSL:1 MANE Select	c.136C>A	p.Pro46Thr	missense	Exon 1 of 5	ENSP00000315137.7	Q8IWX5-1
SGPP2	ENST00000964572.1		c.136C>A	p.Pro46Thr	missense	Exon 1 of 5	ENSP00000634631.1
SGPP2	ENST00000852416.1		c.136C>A	p.Pro46Thr	missense	Exon 1 of 4	ENSP00000522475.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.83e-7

AC:

AN:

1277952

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

627010

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25894

American (AMR)

AF:

0.00

AC:

AN:

22568

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21914

East Asian (EAS)

AF:

0.00

AC:

AN:

27294

South Asian (SAS)

AF:

0.00

AC:

AN:

66692

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31668

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3832

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1025616

Other (OTH)

AF:

0.0000191

AC:

AN:

52474

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

6.8

(source)

DANN

Benign

0.82

DEOGEN2

Benign

0.23

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.049

LIST_S2

Benign

0.45

M_CAP

Uncertain

0.22

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

PhyloP100

0.059

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-0.29

REVEL

Benign

0.0080

Sift

Benign

0.55

Sift4G

Benign

0.23

Polyphen

0.29

Vest4

0.093

MutPred

0.23

Gain of phosphorylation at P46 (P = 0.0277)

MVP

0.37

MPC

0.14

ClinPred

0.15

GERP RS

3.3

PromoterAI

0.058

Neutral

(source)

Varity_R

0.082

gMVP

0.35

Mutation Taster

=95/5

polymorphism

(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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over