rs6109692

Variant names:

• chr20-13091168-C-T
• rs6109692
• NM_018327.4:c.693C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 12 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]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• 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 rank	MANE	Protein	UniProt
SPTLC3	NM_018327.4	c.693C>T	p.Phe231Phe	synonymous_variant	Exon 5 of 12	ENST00000399002.7	NP_060797.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPTLC3	ENST00000399002.7	c.693C>T	p.Phe231Phe	synonymous_variant	Exon 5 of 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

GnomAD2 exomes AF: 0.0936 AC: 23333 AN: 249306 AF XY: 0.0957

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 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

African (AFR) AF: 0.0682 AC: 2283 AN: 33462

American (AMR) AF: 0.0777 AC: 3473 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 2938 AN: 26122

East Asian (EAS) AF: 0.0582 AC: 2309 AN: 39668

South Asian (SAS) AF: 0.0802 AC: 6913 AN: 86216

European-Finnish (FIN) AF: 0.101 AC: 5417 AN: 53404

Middle Eastern (MID) AF: 0.133 AC: 765 AN: 5764

European-Non Finnish (NFE) AF: 0.108 AC: 119499 AN: 1111162

Other (OTH) AF: 0.111 AC: 6718 AN: 60342

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

African (AFR) AF: 0.0679 AC: 2819 AN: 41508

American (AMR) AF: 0.0917 AC: 1400 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 374 AN: 3468

East Asian (EAS) AF: 0.0549 AC: 284 AN: 5176

South Asian (SAS) AF: 0.0759 AC: 365 AN: 4806

European-Finnish (FIN) AF: 0.104 AC: 1100 AN: 10590

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.110 AC: 7481 AN: 68004

Other (OTH) AF: 0.0974 AC: 206 AN: 2114

Alfa AF: 0.103 Hom.: 1680

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
PhyloP100		0.79
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=84/16	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: rs6109692; hg19: chr20-13071816; COSMIC: COSV65468153;