rs12599487

chr16-68400980-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.863

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
SMPD3	NM_018667.4	c.-268-14321T>C		intron_variant		ENST00000219334.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMPD3	ENST00000219334.10	c.-268-14321T>C		intron_variant		1	NM_018667.4	P1
SMPD3	ENST00000561749.1	c.-206-28593T>C		intron_variant		2
SMPD3	ENST00000566723.1	n.91-14321T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.511 AC: 77697 AN: 151938 Hom.: 21771 Cov.: 32

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

Gnomad4 AFR AF: 0.293

Gnomad4 AMR AF: 0.676

Gnomad4 ASJ AF: 0.538

Gnomad4 EAS AF: 0.860

Gnomad4 SAS AF: 0.551

Gnomad4 FIN AF: 0.463

Gnomad4 NFE AF: 0.582

Gnomad4 OTH AF: 0.570

Alfa AF: 0.563 Hom.: 27173

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

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

LitVar

Other links and lift over

dbSNP: rs12599487; hg19: chr16-68434883;