Variant 6-109443332-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_003080.3(SMPD2):c.795G>T(p.Arg265Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 1,612,770 control chromosomes in the GnomAD database, including 162,872 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 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 0.52 ( 21333 hom., cov: 32)

Exomes 𝑓: 0.44 ( 141539 hom. )

Consequence

SMPD2
NM_003080.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.473

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:

SMPD2 (HGNC:):

SMPD2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.225618E-6).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.701 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.795G>T	p.Arg265Ser	missense_variant	9/10	ENST00000258052.8	NP_003071.2	O60906
SMPD2	XM_011536079.2 linkuse as main transcript	c.480G>T	p.Arg160Ser	missense_variant	7/8		XP_011534381.1
SMPD2	XR_942566.3 linkuse as main transcript	n.1128G>T		splice_region_variant, non_coding_transcript_exon_variant	9/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMPD2	ENST00000258052.8 linkuse as main transcript	c.795G>T	p.Arg265Ser	missense_variant	9/10	1	NM_003080.3	ENSP00000258052.3		O60906
SMPD2	ENST00000458487.1 linkuse as main transcript	c.483G>T	p.Arg161Ser	missense_variant	3/4	2		ENSP00000399731.1		H0Y5N2

Frequencies

GnomAD3 genomes

AF:

0.515

AC:

78220

AN:

151858

Hom.:

21293

Cov.:

show subpopulations

Gnomad AFR

AF:

0.708

Gnomad AMI

AF:

0.360

Gnomad AMR

AF:

0.505

Gnomad ASJ

AF:

0.512

Gnomad EAS

AF:

0.486

Gnomad SAS

AF:

0.533

Gnomad FIN

AF:

0.465

Gnomad MID

AF:

0.516

Gnomad NFE

AF:

0.412

Gnomad OTH

AF:

0.489

GnomAD3 exomes

AF:

0.475

AC:

119332

AN:

251394

Hom.:

29291

AF XY:

0.473

AC XY:

64219

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.713

Gnomad AMR exome

AF:

0.490

Gnomad ASJ exome

AF:

0.514

Gnomad EAS exome

AF:

0.470

Gnomad SAS exome

AF:

0.539

Gnomad FIN exome

AF:

0.470

Gnomad NFE exome

AF:

0.418

Gnomad OTH exome

AF:

0.461

GnomAD4 exome

AF:

0.435

AC:

636030

AN:

1460794

Hom.:

141539

Cov.:

AF XY:

0.438

AC XY:

318162

AN XY:

726714

show subpopulations

Gnomad4 AFR exome

AF:

0.716

Gnomad4 AMR exome

AF:

0.489

Gnomad4 ASJ exome

AF:

0.515

Gnomad4 EAS exome

AF:

0.511

Gnomad4 SAS exome

AF:

0.534

Gnomad4 FIN exome

AF:

0.470

Gnomad4 NFE exome

AF:

0.409

Gnomad4 OTH exome

AF:

0.458

GnomAD4 genome

AF:

0.515

AC:

78322

AN:

151976

Hom.:

21333

Cov.:

AF XY:

0.517

AC XY:

38417

AN XY:

74278

show subpopulations

Gnomad4 AFR

AF:

0.708

Gnomad4 AMR

AF:

0.505

Gnomad4 ASJ

AF:

0.512

Gnomad4 EAS

AF:

0.486

Gnomad4 SAS

AF:

0.533

Gnomad4 FIN

AF:

0.465

Gnomad4 NFE

AF:

0.412

Gnomad4 OTH

AF:

0.490

Alfa

AF:

0.431

Hom.:

32560

Bravo

AF:

0.525

TwinsUK

AF:

0.419

AC:

1553

ALSPAC

AF:

0.401

AC:

1546

ESP6500AA

AF:

0.697

AC:

3071

ESP6500EA

AF:

0.422

AC:

3627

ExAC

AF:

0.476

AC:

57854

Asia WGS

AF:

0.538

AC:

1871

AN:

3478

EpiCase

AF:

0.423

EpiControl

AF:

0.424

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.40

CADD

Benign

0.017

DANN

Benign

0.37

DEOGEN2

Benign

0.18

Eigen

Benign

-2.3

Eigen_PC

Benign

-2.3

FATHMM_MKL

Benign

0.048

LIST_S2

Benign

0.11

MetaRNN

Benign

0.0000012

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.55

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.34

REVEL

Benign

0.28

Sift

Benign

0.63

Sift4G

Benign

0.72

Polyphen

0.0

Vest4

0.020

MutPred

0.18

Gain of glycosylation at R265 (P = 0.0019);

MPC

0.083

ClinPred

0.0033

GERP RS

-7.3

Varity_R

0.10

gMVP

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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