20-13137100-A-T

Variant names:

• chr20-13137100-A-T
• rs6105044
• NM_018327.4:c.1279+10383A>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0100

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]

ACMG classification

Verdict is Benign. Variant got -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	c.1279+10383A>T		intron_variant	Intron 9 of 11	ENST00000399002.7	NP_060797.2

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.720 AC: 109422 AN: 151950 Hom.: 39577 Cov.: 32

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.: 32 AF XY: 0.721 AC XY: 53625 AN XY: 74328

Gnomad4 AFR AF: 0.791

Gnomad4 AMR AF: 0.694

Gnomad4 ASJ AF: 0.607

Gnomad4 EAS AF: 0.683

Gnomad4 SAS AF: 0.716

Gnomad4 FIN AF: 0.739

Gnomad4 NFE AF: 0.691

Gnomad4 OTH AF: 0.698

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
DANN	Benign	0.56

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

Other links and lift over

dbSNP: rs6105044; hg19: chr20-13117747;