Genetic Variant NM_006714.5:c.481C>T (chr6-122801319-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -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.

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

Publications

26 publications found

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:

ENSG00000294893 (HGNC:):

ENSG00000294893 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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	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
ENSG00000294893	ENST00000726593.1 link	n.331-19982G>A		intron_variant	Intron 1 of 1
ENSG00000294893	ENST00000726594.1 link	n.314+12984G>A		intron_variant	Intron 2 of 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

GnomAD2 exomes

AF:

0.132

AC:

33065

AN:

251040

AF XY:

0.141

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 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

African (AFR)

AF:

0.0488

AC:

1629

AN:

33412

American (AMR)

AF:

0.0640

AC:

2857

AN:

44670

Ashkenazi Jewish (ASJ)

AF:

0.173

AC:

4510

AN:

26066

East Asian (EAS)

AF:

0.0172

AC:

681

AN:

39684

South Asian (SAS)

AF:

0.228

AC:

19571

AN:

85896

European-Finnish (FIN)

AF:

0.178

AC:

9482

AN:

53408

Middle Eastern (MID)

AF:

0.183

AC:

1050

AN:

5744

European-Non Finnish (NFE)

AF:

0.139

AC:

153926

AN:

1105582

Other (OTH)

AF:

0.135

AC:

8108

AN:

60128

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

6949

13898

20848

27797

34746

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5378

10756

16134

21512

26890

<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:

0.112

AC:

17099

AN:

152236

Hom.:

1158

Cov.:

AF XY:

0.114

AC XY:

8518

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.0467

AC:

1939

AN:

41558

American (AMR)

AF:

0.0845

AC:

1293

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.165

AC:

572

AN:

3468

East Asian (EAS)

AF:

0.0193

AC:

100

AN:

5180

South Asian (SAS)

AF:

0.222

AC:

1072

AN:

4818

European-Finnish (FIN)

AF:

0.182

AC:

1930

AN:

10586

Middle Eastern (MID)

AF:

0.194

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.143

AC:

9703

AN:

68012

Other (OTH)

AF:

0.114

AC:

240

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

789

1578

2368

3157

3946

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

196

392

588

784

980

<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:

0.130

Hom.:

4868

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

(source)

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

PhyloP100

6.6

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

Mutation Taster

=89/11

polymorphism (auto)

(source)

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

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over