Genetic Variant SPTLC3:c.1279+10383A>T (chr20-13137100-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_018327.4(SPTLC3):c.1279+10383A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.72 in 152,068 control chromosomes in the GnomAD database, including 39,626 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 0.72 ( 39626 hom., cov: 32)

Consequence

SPTLC3
NM_018327.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0100

Publications

3 publications found

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:15859): (taspase 1) This gene encodes an endopeptidase that cleaves specific substrates following aspartate residues. The encoded protein undergoes posttranslational autoproteolytic processing to generate alpha and beta subunits, which reassemble into the active alpha2-beta2 heterotetramer. It is required to cleave MLL, a protein required for the maintenance of HOX gene expression, and TFIIA, a basal transcription factor. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

TASP1 Gene-Disease associations (from GenCC):

Suleiman-El-Hattab syndrome
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

TASP1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.784 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPTLC3	NM_018327.4 link	c.1279+10383A>T		intron_variant	Intron 9 of 11	ENST00000399002.7	NP_060797.2	Q9NUV7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPTLC3	ENST00000399002.7 link	c.1279+10383A>T		intron_variant	Intron 9 of 11	1	NM_018327.4	ENSP00000381968.2		Q9NUV7-1
SPTLC3	ENST00000431275.1 link	c.70+10383A>T		intron_variant	Intron 1 of 3	2		ENSP00000409760.1		H0Y733

Frequencies

GnomAD3 genomes

AF:

0.720

AC:

109422

AN:

151950

Hom.:

39577

Cov.:

show subpopulations

Gnomad AFR

AF:

0.791

Gnomad AMI

AF:

0.697

Gnomad AMR

AF:

0.694

Gnomad ASJ

AF:

0.607

Gnomad EAS

AF:

0.683

Gnomad SAS

AF:

0.715

Gnomad FIN

AF:

0.739

Gnomad MID

AF:

0.535

Gnomad NFE

AF:

0.691

Gnomad OTH

AF:

0.700

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

GnomAD4 genome

AF:

0.720

AC:

109534

AN:

152068

Hom.:

39626

Cov.:

AF XY:

0.721

AC XY:

53625

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.791

AC:

32818

AN:

41474

American (AMR)

AF:

0.694

AC:

10603

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.607

AC:

2107

AN:

3470

East Asian (EAS)

AF:

0.683

AC:

3522

AN:

5154

South Asian (SAS)

AF:

0.716

AC:

3446

AN:

4814

European-Finnish (FIN)

AF:

0.739

AC:

7827

AN:

10586

Middle Eastern (MID)

AF:

0.531

AC:

156

AN:

294

European-Non Finnish (NFE)

AF:

0.691

AC:

46943

AN:

67978

Other (OTH)

AF:

0.698

AC:

1478

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1563

3125

4688

6250

7813

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

836

1672

2508

3344

4180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.699

Hom.:

4652

Bravo

AF:

0.720

Asia WGS

AF:

0.741

AC:

2578

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.4

(source)

DANN

Benign

0.56

PhyloP100

-0.010

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over