NM_006714.5:c.113-1925A>G

Variant names:

• chr6-122793752-A-G
• rs11969369
• NM_006714.5:c.113-1925A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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]

ENSG00000294893 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SMPDL3A	NM_006714.5	c.113-1925A>G		intron_variant	Intron 1 of 7	ENST00000368440.5	NP_006705.1
SMPDL3A	NM_001286138.2	c.-67-3072A>G		intron_variant	Intron 1 of 6		NP_001273067.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMPDL3A	ENST00000368440.5	c.113-1925A>G		intron_variant	Intron 1 of 7	1	NM_006714.5	ENSP00000357425.4

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

African (AFR) AF: 0.176 AC: 7307 AN: 41506

American (AMR) AF: 0.240 AC: 3672 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.424 AC: 1471 AN: 3470

East Asian (EAS) AF: 0.166 AC: 858 AN: 5166

South Asian (SAS) AF: 0.460 AC: 2217 AN: 4818

European-Finnish (FIN) AF: 0.458 AC: 4837 AN: 10554

Middle Eastern (MID) AF: 0.408 AC: 119 AN: 292

European-Non Finnish (NFE) AF: 0.336 AC: 22817 AN: 67962

Other (OTH) AF: 0.304 AC: 643 AN: 2112

Alfa AF: 0.306 Hom.: 5127

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
PhyloP100		1.8
Mutation Taster		=100/0	polymorphism (auto)

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: rs11969369; hg19: chr6-123114897;