rs1868158

Positions:

• chr16-68365021-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_018667.4(SMPD3):​c.1395G>A​(p.Pro465Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.594 in 1,613,752 control chromosomes in the GnomAD database, including 287,480 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 0.61 (28567 hom., cov: 32)
  • Exomes 𝑓: 0.59 (258913 hom.)
• Consequence: SMPD3 NM_018667.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.340

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]

SMPD3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP7: Synonymous conserved (PhyloP=-0.34 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMPD3	NM_018667.4	c.1395G>A	p.Pro465Pro	synonymous_variant	4/9	ENST00000219334.10	NP_061137.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMPD3	ENST00000219334.10	c.1395G>A	p.Pro465Pro	synonymous_variant	4/9	1	NM_018667.4	ENSP00000219334.5

Frequencies

GnomAD3 genomes AF: 0.610 AC: 92614 AN: 151926 Hom.: 28536 Cov.: 32

Gnomad AFR AF: 0.655

Gnomad AMI AF: 0.497

Gnomad AMR AF: 0.656

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.785

Gnomad SAS AF: 0.522

Gnomad FIN AF: 0.521

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.589

Gnomad OTH AF: 0.601

GnomAD3 exomes AF: 0.600 AC: 150359 AN: 250656 Hom.: 46016 AF XY: 0.591 AC XY: 80036 AN XY: 135534

Gnomad AFR exome AF: 0.657

Gnomad AMR exome AF: 0.704

Gnomad ASJ exome AF: 0.452

Gnomad EAS exome AF: 0.783

Gnomad SAS exome AF: 0.522

Gnomad FIN exome AF: 0.532

Gnomad NFE exome AF: 0.578

Gnomad OTH exome AF: 0.573

GnomAD4 exome AF: 0.593 AC: 866304 AN: 1461708 Hom.: 258913 Cov.: 62 AF XY: 0.589 AC XY: 428363 AN XY: 727158

Gnomad4 AFR exome AF: 0.661

Gnomad4 AMR exome AF: 0.696

Gnomad4 ASJ exome AF: 0.454

Gnomad4 EAS exome AF: 0.796

Gnomad4 SAS exome AF: 0.527

Gnomad4 FIN exome AF: 0.537

Gnomad4 NFE exome AF: 0.591

Gnomad4 OTH exome AF: 0.585

GnomAD4 genome AF: 0.610 AC: 92689 AN: 152044 Hom.: 28567 Cov.: 32 AF XY: 0.606 AC XY: 44997 AN XY: 74308

Gnomad4 AFR AF: 0.655

Gnomad4 AMR AF: 0.656

Gnomad4 ASJ AF: 0.441

Gnomad4 EAS AF: 0.786

Gnomad4 SAS AF: 0.524

Gnomad4 FIN AF: 0.521

Gnomad4 NFE AF: 0.589

Gnomad4 OTH AF: 0.594

Alfa AF: 0.582 Hom.: 46956

Bravo AF: 0.623

Asia WGS AF: 0.579 AC: 2013 AN: 3478

EpiCase AF: 0.572

EpiControl AF: 0.572

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	4.6
DANN	Benign	0.93

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: rs1868158; hg19: chr16-68398924;