20-13143086-T-G

Variant names:

• chr20-13143086-T-G
• rs17190927
• NM_018327.4:c.1280-10917T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018327.4(SPTLC3):​c.1280-10917T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,254 control chromosomes in the GnomAD database, including 1,110 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 0.11 (1110 hom., cov: 32)
• Consequence: SPTLC3 NM_018327.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.533
• Publications: 11 publications found

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]

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: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018327.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPTLC3	NM_018327.4	MANE Select	c.1280-10917T>G		intron	N/A	NP_060797.2	Q9NUV7-1
	SPTLC3	NM_001349945.2		c.1280-10917T>G		intron	N/A	NP_001336874.1	Q9NUV7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPTLC3	ENST00000399002.7	TSL:1 MANE Select	c.1280-10917T>G		intron	N/A	ENSP00000381968.2	Q9NUV7-1
	SPTLC3	ENST00000966145.1		c.1153-7631T>G		intron	N/A	ENSP00000636204.1
	SPTLC3	ENST00000431275.1	TSL:2	c.71-10917T>G		intron	N/A	ENSP00000409760.1	H0Y733

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17407 AN: 152136 Hom.: 1110 Cov.: 32

Gnomad AFR AF: 0.0627

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.0934

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.0521

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.102

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

GnomAD4 genome AF: 0.114 AC: 17422 AN: 152254 Hom.: 1110 Cov.: 32 AF XY: 0.117 AC XY: 8701 AN XY: 74442

African (AFR) AF: 0.0628 AC: 2610 AN: 41568

American (AMR) AF: 0.169 AC: 2586 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0934 AC: 324 AN: 3470

East Asian (EAS) AF: 0.205 AC: 1058 AN: 5172

South Asian (SAS) AF: 0.0520 AC: 251 AN: 4830

European-Finnish (FIN) AF: 0.153 AC: 1625 AN: 10596

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8608 AN: 68010

Other (OTH) AF: 0.102 AC: 215 AN: 2116

Alfa AF: 0.126 Hom.: 3853

Bravo AF: 0.118

Asia WGS AF: 0.121 AC: 422 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.1
DANN	Benign	0.79
PhyloP100		0.53
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: rs17190927; hg19: chr20-13123733;