Variant chr20-13048957-C-G 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_018327.4(SPTLC3):c.130C>G(p.Pro44Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000399 in 1,553,624 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

SPTLC3
NM_018327.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.346

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:

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=0.023374766).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPTLC3	NM_018327.4 linkuse as main transcript	c.130C>G	p.Pro44Ala	missense_variant	2/12	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.130C>G	p.Pro44Ala	missense_variant	2/12	1	NM_018327.4	ENSP00000381968	P1	Q9NUV7-1
SPTLC3	ENST00000476791.1 linkuse as main transcript	n.419C>G		non_coding_transcript_exon_variant	2/2	1
SPTLC3	ENST00000450297.1 linkuse as main transcript	c.49C>G	p.Pro17Ala	missense_variant	2/5	3		ENSP00000409125
SPTLC3	ENST00000434210.5 linkuse as main transcript	c.130C>G	p.Pro44Ala	missense_variant	3/4	3		ENSP00000389749

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

152076

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000266

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

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:

0.0000441

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.0000686

AC:

AN:

204056

Hom.:

AF XY:

0.0000725

AC XY:

AN XY:

110382

show subpopulations

Gnomad AFR exome

AF:

0.000265

Gnomad AMR exome

AF:

0.000266

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:

0.0000202

Gnomad OTH exome

AF:

0.000431

GnomAD4 exome

AF:

0.0000257

AC:

AN:

1401430

Hom.:

Cov.:

AF XY:

0.0000260

AC XY:

AN XY:

693286

show subpopulations

Gnomad4 AFR exome

AF:

0.000262

Gnomad4 AMR exome

AF:

0.000282

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:

0.00000920

Gnomad4 OTH exome

AF:

0.000156

GnomAD4 genome

AF:

0.000171

AC:

AN:

152194

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.000285

Hom.:

Bravo

AF:

0.000264

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000577

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

Oct 10, 2023

The c.130C>G (p.P44A) alteration is located in exon 2 (coding exon 2) of the SPTLC3 gene. This alteration results from a C to G substitution at nucleotide position 130, causing the proline (P) at amino acid position 44 to be replaced by an alanine (A). 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

0.070

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.29

CADD

Benign

0.66

DANN

Benign

0.33

DEOGEN2

Benign

0.0041

T;T;T

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.53

T;T;T

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.023

T;T;T

MetaSVM

Uncertain

-0.14

MutationAssessor

Benign

0.82

.;L;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.88

N;N;N

REVEL

Benign

0.27

Sift

Benign

0.46

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

.;B;.

Vest4

0.11

MVP

0.48

MPC

0.20

ClinPred

0.011

GERP RS

-6.6

Varity_R

0.017

gMVP

0.26

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