rs41292584

chr6-122809291-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_006714.5(SMPDL3A):c.1245C>T(p.Asp415=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0578 in 1,613,162 control chromosomes in the GnomAD database, including 3,292 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 0.045 (229 hom., cov: 32)
  • Exomes 𝑓: 0.059 (3063 hom.)
• Consequence: SMPDL3A NM_006714.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.378

Genes affected

SMPDL3A (HGNC:17389): (sphingomyelin phosphodiesterase acid like 3A) Enables phosphoric diester hydrolase activity and zinc ion binding activity. Involved in nucleoside triphosphate catabolic process. Located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP7: Synonymous conserved (PhyloP=0.378 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMPDL3A	NM_006714.5	c.1245C>T	p.Asp415=	synonymous_variant	8/8	ENST00000368440.5
SMPDL3A	NM_001286138.2	c.852C>T	p.Asp284=	synonymous_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMPDL3A	ENST00000368440.5	c.1245C>T	p.Asp415=	synonymous_variant	8/8	1	NM_006714.5	P1
SMPDL3A	ENST00000539041.5	c.852C>T	p.Asp284=	synonymous_variant	7/7	2

Frequencies

GnomAD3 genomes AF: 0.0455 AC: 6913 AN: 152100 Hom.: 230 Cov.: 32

Gnomad AFR AF: 0.00944

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.0378

Gnomad ASJ AF: 0.0661

Gnomad EAS AF: 0.0287

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.0760

Gnomad MID AF: 0.0669

Gnomad NFE AF: 0.0574

Gnomad OTH AF: 0.0421

GnomAD3 exomes AF: 0.0576 AC: 14472 AN: 251340 Hom.: 575 AF XY: 0.0633 AC XY: 8607 AN XY: 135874

Gnomad AFR exome AF: 0.00874

Gnomad AMR exome AF: 0.0223

Gnomad ASJ exome AF: 0.0681

Gnomad EAS exome AF: 0.0262

Gnomad SAS exome AF: 0.137

Gnomad FIN exome AF: 0.0716

Gnomad NFE exome AF: 0.0551

Gnomad OTH exome AF: 0.0620

GnomAD4 exome AF: 0.0591 AC: 86316 AN: 1460944 Hom.: 3063 Cov.: 31 AF XY: 0.0618 AC XY: 44911 AN XY: 726838

Gnomad4 AFR exome AF: 0.00932

Gnomad4 AMR exome AF: 0.0233

Gnomad4 ASJ exome AF: 0.0702

Gnomad4 EAS exome AF: 0.0274

Gnomad4 SAS exome AF: 0.140

Gnomad4 FIN exome AF: 0.0721

Gnomad4 NFE exome AF: 0.0561

Gnomad4 OTH exome AF: 0.0575

GnomAD4 genome AF: 0.0454 AC: 6909 AN: 152218 Hom.: 229 Cov.: 32 AF XY: 0.0481 AC XY: 3582 AN XY: 74432

Gnomad4 AFR AF: 0.00941

Gnomad4 AMR AF: 0.0377

Gnomad4 ASJ AF: 0.0661

Gnomad4 EAS AF: 0.0288

Gnomad4 SAS AF: 0.149

Gnomad4 FIN AF: 0.0760

Gnomad4 NFE AF: 0.0574

Gnomad4 OTH AF: 0.0422

Alfa AF: 0.0523 Hom.: 112

Bravo AF: 0.0372

Asia WGS AF: 0.0700 AC: 244 AN: 3478

EpiCase AF: 0.0558

EpiControl AF: 0.0522

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
Cadd	Benign	3.8
Dann	Benign	0.42

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: rs41292584; hg19: chr6-123130436;