dbSNP rs41292584: SMPDL3A:p.Asp415Asp (chr6-122809291-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_006714.5(SMPDL3A):c.1245C>T(p.Asp415Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0578 in 1,613,162 control chromosomes in the GnomAD database, including 3,292 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 0.045 ( 229 hom., cov: 32)

Exomes 𝑓: 0.059 ( 3063 hom. )

Consequence

SMPDL3A
NM_006714.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.378

Publications

8 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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP7

Synonymous conserved (PhyloP=0.378 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMPDL3A	NM_006714.5 link	c.1245C>T	p.Asp415Asp	synonymous_variant	Exon 8 of 8	ENST00000368440.5	NP_006705.1	Q92484-1
SMPDL3A	NM_001286138.2 link	c.852C>T	p.Asp284Asp	synonymous_variant	Exon 7 of 7		NP_001273067.1	Q92484-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SMPDL3A	ENST00000368440.5 link	c.1245C>T	p.Asp415Asp	synonymous_variant	Exon 8 of 8	1	NM_006714.5	ENSP00000357425.4	Q92484-1
SMPDL3A	ENST00000539041.5 link	c.852C>T	p.Asp284Asp	synonymous_variant	Exon 7 of 7	2		ENSP00000442152.1	Q92484-2
ENSG00000294893	ENST00000726593.1 link	n.330+23803G>A		intron_variant	Intron 1 of 1
ENSG00000294893	ENST00000726594.1 link	n.314+5012G>A		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.0455

AC:

6913

AN:

152100

Hom.:

230

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00944

Gnomad AMI

AF:

0.0329

Gnomad AMR

AF:

0.0378

Gnomad ASJ

AF:

0.0661

Gnomad EAS

AF:

0.0287

Gnomad SAS

AF:

0.149

Gnomad FIN

AF:

0.0760

Gnomad MID

AF:

0.0669

Gnomad NFE

AF:

0.0574

Gnomad OTH

AF:

0.0421

GnomAD2 exomes

AF:

0.0576

AC:

14472

AN:

251340

AF XY:

0.0633

show subpopulations

Gnomad AFR exome

AF:

0.00874

Gnomad AMR exome

AF:

0.0223

Gnomad ASJ exome

AF:

0.0681

Gnomad EAS exome

AF:

0.0262

Gnomad FIN exome

AF:

0.0716

Gnomad NFE exome

AF:

0.0551

Gnomad OTH exome

AF:

0.0620

GnomAD4 exome

AF:

0.0591

AC:

86316

AN:

1460944

Hom.:

3063

Cov.:

AF XY:

0.0618

AC XY:

44911

AN XY:

726838

show subpopulations

African (AFR)

AF:

0.00932

AC:

312

AN:

33472

American (AMR)

AF:

0.0233

AC:

1042

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0702

AC:

1834

AN:

26132

East Asian (EAS)

AF:

0.0274

AC:

1088

AN:

39684

South Asian (SAS)

AF:

0.140

AC:

12058

AN:

86240

European-Finnish (FIN)

AF:

0.0721

AC:

3852

AN:

53416

Middle Eastern (MID)

AF:

0.0583

AC:

336

AN:

5764

European-Non Finnish (NFE)

AF:

0.0561

AC:

62323

AN:

1111160

Other (OTH)

AF:

0.0575

AC:

3471

AN:

60354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

4062

8124

12187

16249

20311

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2346

4692

7038

9384

11730

<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:

0.0454

AC:

6909

AN:

152218

Hom.:

229

Cov.:

AF XY:

0.0481

AC XY:

3582

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.00941

AC:

391

AN:

41546

American (AMR)

AF:

0.0377

AC:

577

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0661

AC:

229

AN:

3466

East Asian (EAS)

AF:

0.0288

AC:

149

AN:

5180

South Asian (SAS)

AF:

0.149

AC:

719

AN:

4826

European-Finnish (FIN)

AF:

0.0760

AC:

804

AN:

10584

Middle Eastern (MID)

AF:

0.0651

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0574

AC:

3902

AN:

68002

Other (OTH)

AF:

0.0422

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

336

672

1008

1344

1680

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

192

288

384

480

<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:

0.0523

Hom.:

112

Bravo

AF:

0.0372

Asia WGS

AF:

0.0700

AC:

244

AN:

3478

EpiCase

AF:

0.0558

EpiControl

AF:

0.0522

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

3.8

(source)

DANN

Benign

0.42

PhyloP100

0.38

Mutation Taster

=100/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over