Variant 6-122789365-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006714.5(SMPDL3A):c.19C>T(p.Leu7Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000129 in 1,395,146 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

SMPDL3A
NM_006714.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.279

Variant links:

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 links:

SMPDL3A (HGNC:):

SMPDL3A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.039587528).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMPDL3A	NM_006714.5 linkuse as main transcript	c.19C>T	p.Leu7Phe	missense_variant	1/8	ENST00000368440.5	NP_006705.1	Q92484-1
SMPDL3A	NM_001286138.2 linkuse as main transcript	c.-161C>T		5_prime_UTR_variant	1/7		NP_001273067.1	Q92484-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SMPDL3A	ENST00000368440.5 linkuse as main transcript	c.19C>T	p.Leu7Phe	missense_variant	1/8	1	NM_006714.5	ENSP00000357425.4	Q92484-1
SMPDL3A	ENST00000539041 linkuse as main transcript	c.-161C>T		5_prime_UTR_variant	1/7	2		ENSP00000442152.1	Q92484-2
SMPDL3A	ENST00000487215.1 linkuse as main transcript	n.74C>T		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000837

AC:

AN:

143314

Hom.:

AF XY:

0.0000130

AC XY:

AN XY:

77144

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000492

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000129

AC:

AN:

1395146

Hom.:

Cov.:

AF XY:

0.00000727

AC XY:

AN XY:

688028

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000505

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000936

Hom.:

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 17, 2024

The c.19C>T (p.L7F) alteration is located in exon 1 (coding exon 1) of the SMPDL3A gene. This alteration results from a C to T substitution at nucleotide position 19, causing the leucine (L) at amino acid position 7 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.72

CADD

Benign

7.6

DANN

Benign

0.89

DEOGEN2

Benign

0.019

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.052

LIST_S2

Benign

0.53

M_CAP

Benign

0.0059

MetaRNN

Benign

0.040

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.69

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.30

REVEL

Benign

0.015

Sift

Benign

0.30

Sift4G

Benign

0.13

Polyphen

0.0050

Vest4

0.052

MutPred

0.40

Loss of helix (P = 0.0626);

MVP

0.085

MPC

0.095

ClinPred

0.022

GERP RS

0.54

Varity_R

0.049

gMVP

0.24

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over