rs8050499

Variant names:

• chr16-68394423-A-C
• rs8050499
• NM_018667.4:c.-268-7764T>G

Your query was ambiguous. Multiple possible variants found:

• chr16-68394423-A-C
• chr16-68394423-A-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018667.4(SMPD3):​c.-268-7764T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: SMPD3 NM_018667.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0250
• Publications: 11 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMPD3	NM_018667.4	c.-268-7764T>G		intron_variant	Intron 1 of 8	ENST00000219334.10	NP_061137.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMPD3	ENST00000219334.10	c.-268-7764T>G		intron_variant	Intron 1 of 8	1	NM_018667.4	ENSP00000219334.5
SMPD3	ENST00000561749.1	c.-206-22036T>G		intron_variant	Intron 1 of 1	2		ENSP00000457236.1
SMPD3	ENST00000566723.1	n.91-7764T>G		intron_variant	Intron 1 of 4	4

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 6942

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.55
PhyloP100		0.025

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

Other links and lift over

dbSNP: rs8050499; hg19: chr16-68428326;