rs11969369

Positions:

• chr6-122793752-A-G

Variant summary

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

The NM_006714.5(SMPDL3A):​c.113-1925A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 152,086 control chromosomes in the GnomAD database, including 7,279 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 0.29 (7279 hom., cov: 32)
• Consequence: SMPDL3A NM_006714.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.76

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]

SMPDL3A (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMPDL3A	NM_006714.5	c.113-1925A>G		intron_variant		ENST00000368440.5	NP_006705.1
SMPDL3A	NM_001286138.2	c.-67-3072A>G		intron_variant			NP_001273067.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMPDL3A	ENST00000368440.5	c.113-1925A>G		intron_variant		1	NM_006714.5	ENSP00000357425.4
SMPDL3A	ENST00000539041.5	c.-67-3072A>G		intron_variant		2		ENSP00000442152.1
SMPDL3A	ENST00000487215.1	n.168-1925A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44379 AN: 151968 Hom.: 7278 Cov.: 32

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.424

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.459

Gnomad FIN AF: 0.458

Gnomad MID AF: 0.401

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.304

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

GnomAD4 genome AF: 0.292 AC: 44407 AN: 152086 Hom.: 7279 Cov.: 32 AF XY: 0.301 AC XY: 22355 AN XY: 74358

Gnomad4 AFR AF: 0.176

Gnomad4 AMR AF: 0.240

Gnomad4 ASJ AF: 0.424

Gnomad4 EAS AF: 0.166

Gnomad4 SAS AF: 0.460

Gnomad4 FIN AF: 0.458

Gnomad4 NFE AF: 0.336

Gnomad4 OTH AF: 0.304

Alfa AF: 0.300 Hom.: 3498

Bravo AF: 0.263

Asia WGS AF: 0.272 AC: 943 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	14
DANN	Benign	0.65

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: rs11969369; hg19: chr6-123114897;