chr16-68400980-A-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_018667.4(SMPD3):​c.-268-14321T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.511 in 152,056 control chromosomes in the GnomAD database, including 21,785 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 0.51 ( 21785 hom., cov: 32)

Consequence

SMPD3
NM_018667.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.863

Publications

11 publications found
Variant links:
Genes affected
SMPD3 (HGNC:14240): (sphingomyelin phosphodiesterase 3) Predicted to enable phosphatidic acid binding activity; phosphatidylserine binding activity; and sphingomyelin phosphodiesterase activity. Predicted to be involved in positive regulation of exosomal secretion and sphingomyelin metabolic process. Predicted to act upstream of or within several processes, including animal organ development; enzyme linked receptor protein signaling pathway; and sphingolipid metabolic process. Predicted to be located in Golgi apparatus and plasma membrane. Predicted to be active in cytoplasm. Biomarker of pulmonary emphysema. [provided by Alliance of Genome Resources, Apr 2022]

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 (BayesDel_noAF=-0.71).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.839 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SMPD3NM_018667.4 linkc.-268-14321T>C intron_variant Intron 1 of 8 ENST00000219334.10 NP_061137.1 Q9NY59-1A8K0T6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SMPD3ENST00000219334.10 linkc.-268-14321T>C intron_variant Intron 1 of 8 1 NM_018667.4 ENSP00000219334.5 Q9NY59-1
SMPD3ENST00000561749.1 linkc.-206-28593T>C intron_variant Intron 1 of 1 2 ENSP00000457236.1 H3BTM0
SMPD3ENST00000566723.1 linkn.91-14321T>C intron_variant Intron 1 of 4 4

Frequencies

GnomAD3 genomes
AF:
0.511
AC:
77697
AN:
151938
Hom.:
21771
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.293
Gnomad AMI
AF:
0.578
Gnomad AMR
AF:
0.675
Gnomad ASJ
AF:
0.538
Gnomad EAS
AF:
0.859
Gnomad SAS
AF:
0.550
Gnomad FIN
AF:
0.463
Gnomad MID
AF:
0.551
Gnomad NFE
AF:
0.582
Gnomad OTH
AF:
0.567
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.511
AC:
77737
AN:
152056
Hom.:
21785
Cov.:
32
AF XY:
0.512
AC XY:
38034
AN XY:
74344
show subpopulations
African (AFR)
AF:
0.293
AC:
12140
AN:
41472
American (AMR)
AF:
0.676
AC:
10323
AN:
15276
Ashkenazi Jewish (ASJ)
AF:
0.538
AC:
1868
AN:
3472
East Asian (EAS)
AF:
0.860
AC:
4454
AN:
5178
South Asian (SAS)
AF:
0.551
AC:
2654
AN:
4818
European-Finnish (FIN)
AF:
0.463
AC:
4887
AN:
10566
Middle Eastern (MID)
AF:
0.531
AC:
156
AN:
294
European-Non Finnish (NFE)
AF:
0.582
AC:
39530
AN:
67966
Other (OTH)
AF:
0.570
AC:
1200
AN:
2106
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.499
Heterozygous variant carriers
0
1800
3599
5399
7198
8998
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
686
1372
2058
2744
3430
<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:
0.558
Hom.:
39589
Bravo
AF:
0.521
Asia WGS
AF:
0.646
AC:
2244
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.71
CADD
Benign
8.1
DANN
Benign
0.88
PhyloP100
0.86
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs12599487; hg19: chr16-68434883; API