rs6041859

Positions:

• chr20-13102045-C-T

Variant summary

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

The NM_018327.4(SPTLC3):​c.827-8067C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.762 in 152,056 control chromosomes in the GnomAD database, including 45,223 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 0.76 (45223 hom., cov: 31)
• Consequence: SPTLC3 NM_018327.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0110

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.932 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPTLC3	NM_018327.4	c.827-8067C>T		intron_variant		ENST00000399002.7	NP_060797.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPTLC3	ENST00000399002.7	c.827-8067C>T		intron_variant		1	NM_018327.4	ENSP00000381968	P1

Frequencies

GnomAD3 genomes AF: 0.762 AC: 115743 AN: 151938 Hom.: 45172 Cov.: 31

Gnomad AFR AF: 0.940

Gnomad AMI AF: 0.689

Gnomad AMR AF: 0.777

Gnomad ASJ AF: 0.690

Gnomad EAS AF: 0.593

Gnomad SAS AF: 0.571

Gnomad FIN AF: 0.625

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.702

Gnomad OTH AF: 0.758

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

GnomAD4 genome AF: 0.762 AC: 115853 AN: 152056 Hom.: 45223 Cov.: 31 AF XY: 0.755 AC XY: 56066 AN XY: 74298

Gnomad4 AFR AF: 0.940

Gnomad4 AMR AF: 0.777

Gnomad4 ASJ AF: 0.690

Gnomad4 EAS AF: 0.591

Gnomad4 SAS AF: 0.570

Gnomad4 FIN AF: 0.625

Gnomad4 NFE AF: 0.702

Gnomad4 OTH AF: 0.759

Alfa AF: 0.738 Hom.: 5250

Bravo AF: 0.782

Asia WGS AF: 0.600 AC: 2084 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.5
DANN	Benign	0.67

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: rs6041859; hg19: chr20-13082692;