rs6109692

Positions:

• chr20-13091168-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6 BP7 BA1

The NM_018327.4(SPTLC3):​c.693C>T​(p.Phe231Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 1,612,992 control chromosomes in the GnomAD database, including 8,756 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.093 (751 hom., cov: 32)
  • Exomes 𝑓: 0.10 (8005 hom.)
• Consequence: SPTLC3 NM_018327.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.785

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=-0.28).
• BP6: Variant 20-13091168-C-T is Benign according to our data. Variant chr20-13091168-C-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=0.785 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPTLC3	NM_018327.4	c.693C>T	p.Phe231Phe	synonymous_variant	5/12	ENST00000399002.7	NP_060797.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPTLC3	ENST00000399002.7	c.693C>T	p.Phe231Phe	synonymous_variant	5/12	1	NM_018327.4	ENSP00000381968.2

Frequencies

GnomAD3 genomes AF: 0.0935 AC: 14221 AN: 152024 Hom.: 751 Cov.: 32

Gnomad AFR AF: 0.0679

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.0918

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.0545

Gnomad SAS AF: 0.0761

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.0985

GnomAD3 exomes AF: 0.0936 AC: 23333 AN: 249306 Hom.: 1200 AF XY: 0.0957 AC XY: 12939 AN XY: 135258

Gnomad AFR exome AF: 0.0679

Gnomad AMR exome AF: 0.0763

Gnomad ASJ exome AF: 0.111

Gnomad EAS exome AF: 0.0509

Gnomad SAS exome AF: 0.0831

Gnomad FIN exome AF: 0.0992

Gnomad NFE exome AF: 0.109

Gnomad OTH exome AF: 0.105

GnomAD4 exome AF: 0.103 AC: 150315 AN: 1460850 Hom.: 8005 Cov.: 31 AF XY: 0.103 AC XY: 74518 AN XY: 726714

Gnomad4 AFR exome AF: 0.0682

Gnomad4 AMR exome AF: 0.0777

Gnomad4 ASJ exome AF: 0.112

Gnomad4 EAS exome AF: 0.0582

Gnomad4 SAS exome AF: 0.0802

Gnomad4 FIN exome AF: 0.101

Gnomad4 NFE exome AF: 0.108

Gnomad4 OTH exome AF: 0.111

GnomAD4 genome AF: 0.0935 AC: 14223 AN: 152142 Hom.: 751 Cov.: 32 AF XY: 0.0936 AC XY: 6961 AN XY: 74378

Gnomad4 AFR AF: 0.0679

Gnomad4 AMR AF: 0.0917

Gnomad4 ASJ AF: 0.108

Gnomad4 EAS AF: 0.0549

Gnomad4 SAS AF: 0.0759

Gnomad4 FIN AF: 0.104

Gnomad4 NFE AF: 0.110

Gnomad4 OTH AF: 0.0974

Alfa AF: 0.104 Hom.: 1404

Bravo AF: 0.0903

Asia WGS AF: 0.0750 AC: 263 AN: 3478

EpiCase AF: 0.111

EpiControl AF: 0.108

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	11
DANN	Benign	0.67
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs6109692; hg19: chr20-13071816; COSMIC: COSV65468153;