rs10512220

Positions:

• chr9-92044049-T-C

Variant summary

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

The NM_006415.4(SPTLC1):​c.1136+1950A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 151,994 control chromosomes in the GnomAD database, including 24,789 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 (24789 hom., cov: 31)
• Consequence: SPTLC1 NM_006415.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.78

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.841 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPTLC1	NM_006415.4	c.1136+1950A>G		intron_variant		ENST00000262554.7	NP_006406.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPTLC1	ENST00000262554.7	c.1136+1950A>G		intron_variant		1	NM_006415.4	ENSP00000262554.2

Frequencies

GnomAD3 genomes AF: 0.533 AC: 80908 AN: 151876 Hom.: 24734 Cov.: 31

Gnomad AFR AF: 0.848

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.515

Gnomad EAS AF: 0.434

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.496

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

GnomAD4 genome AF: 0.533 AC: 81025 AN: 151994 Hom.: 24789 Cov.: 31 AF XY: 0.534 AC XY: 39641 AN XY: 74284

Gnomad4 AFR AF: 0.848

Gnomad4 AMR AF: 0.569

Gnomad4 ASJ AF: 0.515

Gnomad4 EAS AF: 0.434

Gnomad4 SAS AF: 0.454

Gnomad4 FIN AF: 0.376

Gnomad4 NFE AF: 0.374

Gnomad4 OTH AF: 0.498

Alfa AF: 0.465 Hom.: 2340

Bravo AF: 0.560

Asia WGS AF: 0.489 AC: 1705 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.0090
DANN	Benign	0.59

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: rs10512220; hg19: chr9-94806331;