16-68394423-A-G

Position:

• chr16-68394423-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.-268-7764T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 152,094 control chromosomes in the GnomAD database, including 2,646 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 0.18 (2646 hom., cov: 33)
• Consequence: SMPD3 NM_018667.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0250

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMPD3	NM_018667.4	c.-268-7764T>C		intron_variant		ENST00000219334.10	NP_061137.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMPD3	ENST00000219334.10	c.-268-7764T>C		intron_variant		1	NM_018667.4	ENSP00000219334.5
SMPD3	ENST00000561749.1	c.-206-22036T>C		intron_variant		2		ENSP00000457236.1
SMPD3	ENST00000566723.1	n.91-7764T>C		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27378 AN: 151976 Hom.: 2638 Cov.: 33

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.0694

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.179

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

GnomAD4 genome AF: 0.180 AC: 27407 AN: 152094 Hom.: 2646 Cov.: 33 AF XY: 0.185 AC XY: 13740 AN XY: 74358

Gnomad4 AFR AF: 0.209

Gnomad4 AMR AF: 0.138

Gnomad4 ASJ AF: 0.202

Gnomad4 EAS AF: 0.0692

Gnomad4 SAS AF: 0.182

Gnomad4 FIN AF: 0.249

Gnomad4 NFE AF: 0.168

Gnomad4 OTH AF: 0.185

Alfa AF: 0.165 Hom.: 4430

Bravo AF: 0.171

Asia WGS AF: 0.173 AC: 603 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.54

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: rs8050499; hg19: chr16-68428326;