Variant 20-13126597-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018327.4(SPTLC3):c.1159G>A(p.Val387Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000273 in 1,613,152 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

SPTLC3
NM_018327.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.54

Variant links:

Genes affected

SPTLC3 (HGNC:16253): (serine palmitoyltransferase long chain base subunit 3) This gene encodes a subunit of the serine palmitoyltransferase complex which catalyzes the rate-limiting step in sphingolipid biosynthesis. This subunit metabolizes lauroyl- and myristoyl-CoA and generates C14 and C16-sphingoid bases. [provided by RefSeq, Mar 2017]

SPTLC3 links:

TASP1 (HGNC:):

TASP1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPTLC3	NM_018327.4 linkuse as main transcript	c.1159G>A	p.Val387Met	missense_variant	9/12	ENST00000399002.7	NP_060797.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPTLC3	ENST00000399002.7 linkuse as main transcript	c.1159G>A	p.Val387Met	missense_variant	9/12	1	NM_018327.4	ENSP00000381968	P1	Q9NUV7-1
SPTLC3	ENST00000431275.1 linkuse as main transcript			upstream_gene_variant		2		ENSP00000409760

Frequencies

GnomAD3 genomes

AF:

0.0000921

AC:

AN:

152074

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000322

AC:

AN:

248274

Hom.:

AF XY:

0.0000297

AC XY:

AN XY:

134582

show subpopulations

Gnomad AFR exome

AF:

0.000194

Gnomad AMR exome

AF:

0.0000583

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:

0.0000266

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000205

AC:

AN:

1461078

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

726778

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.0000673

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000189

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000921

AC:

AN:

152074

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74248

show subpopulations

Gnomad4 AFR

AF:

0.000314

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000161

Hom.:

Bravo

AF:

0.0000907

ESP6500AA

AF:

0.000268

AC:

ESP6500EA

AF:

0.000122

AC:

ExAC

AF:

0.0000331

AC:

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

Dec 06, 2021

The c.1159G>A (p.V387M) alteration is located in exon 9 (coding exon 9) of the SPTLC3 gene. This alteration results from a G to A substitution at nucleotide position 1159, causing the valine (V) at amino acid position 387 to be replaced by a methionine (M). 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

0.33

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Pathogenic

0.19

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.51

Eigen

Pathogenic

0.84

Eigen_PC

Pathogenic

0.81

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.91

M_CAP

Uncertain

0.11

MetaRNN

Uncertain

0.63

MetaSVM

Pathogenic

0.94

MutationAssessor

Uncertain

2.7

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-2.4

REVEL

Uncertain

0.57

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.53

MVP

0.85

MPC

0.79

ClinPred

0.81

GERP RS

6.2

Varity_R

0.75

gMVP

0.86

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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