rs2297568

Positions:

• chr9-92112369-G-A
• chr9-92112369-G-C

Variant summary

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

The NM_006415.4(SPTLC1):​c.165+86C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 955,390 control chromosomes in the GnomAD database, including 96,748 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 0.53 (24583 hom., cov: 32)
  • Exomes 𝑓: 0.41 (72165 hom.)
• Consequence: SPTLC1 NM_006415.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.819

Genes affected

SPTLC1 (HGNC:11277): (serine palmitoyltransferase long chain base subunit 1) This gene encodes a member of the class-II pyridoxal-phosphate-dependent aminotransferase family. The encoded protein is the long chain base subunit 1 of serine palmitoyltransferase. Serine palmitoyltransferase converts L-serine and palmitoyl-CoA to 3-oxosphinganine with pyridoxal 5'-phosphate and is the key enzyme in sphingolipid biosynthesis. Mutations in this gene were identified in patients with hereditary sensory neuropathy type 1. Alternatively spliced variants encoding different isoforms have been identified. Pseudogenes of this gene have been defined on chromosomes 1, 6, 10, and 13. [provided by RefSeq, Jul 2013]

SPTLC1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.838 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPTLC1	NM_006415.4	c.165+86C>T		intron_variant		ENST00000262554.7	NP_006406.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPTLC1	ENST00000262554.7	c.165+86C>T		intron_variant		1	NM_006415.4	ENSP00000262554.2

Frequencies

GnomAD3 genomes AF: 0.530 AC: 80547 AN: 151928 Hom.: 24536 Cov.: 32

Gnomad AFR AF: 0.845

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.568

Gnomad ASJ AF: 0.515

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.492

GnomAD4 exome AF: 0.413 AC: 332077 AN: 803344 Hom.: 72165 AF XY: 0.412 AC XY: 173909 AN XY: 421782

Gnomad4 AFR exome AF: 0.855

Gnomad4 AMR exome AF: 0.586

Gnomad4 ASJ exome AF: 0.515

Gnomad4 EAS exome AF: 0.408

Gnomad4 SAS exome AF: 0.456

Gnomad4 FIN exome AF: 0.377

Gnomad4 NFE exome AF: 0.375

Gnomad4 OTH exome AF: 0.440

GnomAD4 genome AF: 0.530 AC: 80653 AN: 152046 Hom.: 24583 Cov.: 32 AF XY: 0.531 AC XY: 39419 AN XY: 74288

Gnomad4 AFR AF: 0.846

Gnomad4 AMR AF: 0.567

Gnomad4 ASJ AF: 0.515

Gnomad4 EAS AF: 0.433

Gnomad4 SAS AF: 0.451

Gnomad4 FIN AF: 0.371

Gnomad4 NFE AF: 0.371

Gnomad4 OTH AF: 0.494

Alfa AF: 0.469 Hom.: 3041

Bravo AF: 0.558

Asia WGS AF: 0.490 AC: 1706 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.2
DANN	Benign	0.77

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: rs2297568; hg19: chr9-94874651;