Variant rs1048197 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000258052.8(SMPD2):c.8C>T(p.Pro3Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0505 in 1,614,028 control chromosomes in the GnomAD database, including 3,581 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.060 ( 410 hom., cov: 32)

Exomes 𝑓: 0.049 ( 3171 hom. )

Consequence

SMPD2
ENST00000258052.8 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0580

Variant links:

Genes affected

SMPD2 (HGNC:11121): (sphingomyelin phosphodiesterase 2) This gene encodes a protein which was initially identified as a sphingomyelinase based on sequence similarity between bacterial sphingomyelinases and a yeast protein. Subsequent studies showed that its biological function is less likely to be as a sphingomyelinase and instead as a lysophospholipase. [provided by RefSeq, Oct 2009]

SMPD2 links:

PPIL6 (HGNC:21557): (peptidylprolyl isomerase like 6) Predicted to enable peptidyl-prolyl cis-trans isomerase activity. Predicted to be involved in protein folding and protein peptidyl-prolyl isomerization. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

PPIL6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0012243986).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMPD2	NM_003080.3 linkuse as main transcript	c.8C>T	p.Pro3Leu	missense_variant	1/10	ENST00000258052.8	NP_003071.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMPD2	ENST00000258052.8 linkuse as main transcript	c.8C>T	p.Pro3Leu	missense_variant	1/10	1	NM_003080.3	ENSP00000258052	P1
PPIL6	ENST00000440797.6 linkuse as main transcript	c.-539G>A		5_prime_UTR_variant	1/9	1		ENSP00000392257		Q8IXY8-2
PPIL6	ENST00000424445.6 linkuse as main transcript	c.-539G>A		5_prime_UTR_variant	1/7	5		ENSP00000407731		Q8IXY8-3

Frequencies

GnomAD3 genomes

AF:

0.0603

AC:

9176

AN:

152148

Hom.:

409

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0546

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.118

Gnomad ASJ

AF:

0.0426

Gnomad EAS

AF:

0.204

Gnomad SAS

AF:

0.137

Gnomad FIN

AF:

0.0744

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.0337

Gnomad OTH

AF:

0.0621

GnomAD3 exomes

AF:

0.0794

AC:

19951

AN:

251324

Hom.:

1294

AF XY:

0.0770

AC XY:

10468

AN XY:

135862

show subpopulations

Gnomad AFR exome

AF:

0.0553

Gnomad AMR exome

AF:

0.157

Gnomad ASJ exome

AF:

0.0459

Gnomad EAS exome

AF:

0.185

Gnomad SAS exome

AF:

0.128

Gnomad FIN exome

AF:

0.0693

Gnomad NFE exome

AF:

0.0351

Gnomad OTH exome

AF:

0.0624

GnomAD4 exome

AF:

0.0494

AC:

72251

AN:

1461762

Hom.:

3171

Cov.:

AF XY:

0.0511

AC XY:

37123

AN XY:

727184

show subpopulations

Gnomad4 AFR exome

AF:

0.0525

Gnomad4 AMR exome

AF:

0.152

Gnomad4 ASJ exome

AF:

0.0453

Gnomad4 EAS exome

AF:

0.205

Gnomad4 SAS exome

AF:

0.126

Gnomad4 FIN exome

AF:

0.0656

Gnomad4 NFE exome

AF:

0.0324

Gnomad4 OTH exome

AF:

0.0604

GnomAD4 genome

AF:

0.0604

AC:

9196

AN:

152266

Hom.:

410

Cov.:

AF XY:

0.0666

AC XY:

4955

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.0546

Gnomad4 AMR

AF:

0.119

Gnomad4 ASJ

AF:

0.0426

Gnomad4 EAS

AF:

0.204

Gnomad4 SAS

AF:

0.137

Gnomad4 FIN

AF:

0.0744

Gnomad4 NFE

AF:

0.0337

Gnomad4 OTH

AF:

0.0619

Alfa

AF:

0.0438

Hom.:

554

Bravo

AF:

0.0636

TwinsUK

AF:

0.0329

AC:

122

ALSPAC

AF:

0.0332

AC:

128

ESP6500AA

AF:

0.0545

AC:

240

ESP6500EA

AF:

0.0360

AC:

310

ExAC

AF:

0.0748

AC:

9082

Asia WGS

AF:

0.178

AC:

617

AN:

3478

EpiCase

AF:

0.0399

EpiControl

AF:

0.0395

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.22

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.63

MetaRNN

Benign

0.0012

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

MutationTaster

Benign

1.4e-16

P;P;P;P

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.64

REVEL

Benign

0.060

Sift

Benign

0.17

Sift4G

Benign

0.40

Polyphen

0.011

Vest4

0.050

MPC

0.076

ClinPred

0.034

GERP RS

4.3

Varity_R

0.057

gMVP

0.46

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over