Genetic Variant SMPDL3A:p.Pro161Ser (chr6-122801319-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_006714.5(SMPDL3A):c.481C>T(p.Pro161Ser) variant causes a missense change. The variant allele was found at a frequency of 0.136 in 1,606,826 control chromosomes in the GnomAD database, including 16,747 homozygotes. In-silico tool predicts 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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.11 ( 1158 hom., cov: 33)

Exomes 𝑓: 0.14 ( 15589 hom. )

Consequence

SMPDL3A
NM_006714.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.57

Variant links:

Genes affected

SMPDL3A (HGNC:17389): (sphingomyelin phosphodiesterase acid like 3A) Enables phosphoric diester hydrolase activity and zinc ion binding activity. Involved in nucleoside triphosphate catabolic process. Located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

SMPDL3A 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=0.0019767582).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMPDL3A	NM_006714.5 link	c.481C>T	p.Pro161Ser	missense_variant	Exon 4 of 8	ENST00000368440.5	NP_006705.1	Q92484-1
SMPDL3A	NM_001286138.2 link	c.88C>T	p.Pro30Ser	missense_variant	Exon 3 of 7		NP_001273067.1	Q92484-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMPDL3A	ENST00000368440.5 link	c.481C>T	p.Pro161Ser	missense_variant	Exon 4 of 8	1	NM_006714.5	ENSP00000357425.4		Q92484-1
SMPDL3A	ENST00000539041.5 link	c.88C>T	p.Pro30Ser	missense_variant	Exon 3 of 7	2		ENSP00000442152.1		Q92484-2

Frequencies

GnomAD3 genomes

AF:

0.112

AC:

17097

AN:

152118

Hom.:

1161

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0466

Gnomad AMI

AF:

0.212

Gnomad AMR

AF:

0.0847

Gnomad ASJ

AF:

0.165

Gnomad EAS

AF:

0.0195

Gnomad SAS

AF:

0.222

Gnomad FIN

AF:

0.182

Gnomad MID

AF:

0.199

Gnomad NFE

AF:

0.143

Gnomad OTH

AF:

0.114

GnomAD3 exomes

AF:

0.132

AC:

33065

AN:

251040

Hom.:

2758

AF XY:

0.141

AC XY:

19071

AN XY:

135656

show subpopulations

Gnomad AFR exome

AF:

0.0457

Gnomad AMR exome

AF:

0.0606

Gnomad ASJ exome

AF:

0.175

Gnomad EAS exome

AF:

0.0158

Gnomad SAS exome

AF:

0.231

Gnomad FIN exome

AF:

0.176

Gnomad NFE exome

AF:

0.146

Gnomad OTH exome

AF:

0.132

GnomAD4 exome

AF:

0.139

AC:

201814

AN:

1454590

Hom.:

15589

Cov.:

AF XY:

0.142

AC XY:

102915

AN XY:

723952

show subpopulations

Gnomad4 AFR exome

AF:

0.0488

Gnomad4 AMR exome

AF:

0.0640

Gnomad4 ASJ exome

AF:

0.173

Gnomad4 EAS exome

AF:

0.0172

Gnomad4 SAS exome

AF:

0.228

Gnomad4 FIN exome

AF:

0.178

Gnomad4 NFE exome

AF:

0.139

Gnomad4 OTH exome

AF:

0.135

GnomAD4 genome

AF:

0.112

AC:

17099

AN:

152236

Hom.:

1158

Cov.:

AF XY:

0.114

AC XY:

8518

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.0467

Gnomad4 AMR

AF:

0.0845

Gnomad4 ASJ

AF:

0.165

Gnomad4 EAS

AF:

0.0193

Gnomad4 SAS

AF:

0.222

Gnomad4 FIN

AF:

0.182

Gnomad4 NFE

AF:

0.143

Gnomad4 OTH

AF:

0.114

Alfa

AF:

0.130

Hom.:

2328

Bravo

AF:

0.0991

TwinsUK

AF:

0.144

AC:

534

ALSPAC

AF:

0.140

AC:

538

ESP6500AA

AF:

0.0461

AC:

203

ESP6500EA

AF:

0.146

AC:

1253

ExAC

AF:

0.135

AC:

16382

Asia WGS

AF:

0.115

AC:

401

AN:

3478

EpiCase

AF:

0.147

EpiControl

AF:

0.142

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.52

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Uncertain

-0.040

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.46

.;T

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.89

D;D

MetaRNN

Benign

0.0020

T;T

MetaSVM

Uncertain

0.19

MutationAssessor

Uncertain

2.5

.;M

PrimateAI

Uncertain

0.49

PROVEAN

Pathogenic

-7.5

D;D

REVEL

Uncertain

0.43

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

.;D

Vest4

0.44

MPC

0.48

ClinPred

0.038

GERP RS

5.7

Varity_R

0.89

gMVP

0.86

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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