rs10512220

Variant names:

• chr9-92044049-T-C
• rs10512220
• NM_006415.4:c.1136+1950A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• amyotrophic lateral sclerosis 27, juvenile

  Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• neuropathy, hereditary sensory and autonomic, type 1A

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• hereditary sensory and autonomic neuropathy type 1

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SPTLC1	NM_006415.4	c.1136+1950A>G		intron_variant	Intron 12 of 14	ENST00000262554.7	NP_006406.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPTLC1	ENST00000262554.7	c.1136+1950A>G		intron_variant	Intron 12 of 14	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

African (AFR) AF: 0.848 AC: 35183 AN: 41472

American (AMR) AF: 0.569 AC: 8688 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.515 AC: 1788 AN: 3470

East Asian (EAS) AF: 0.434 AC: 2242 AN: 5164

South Asian (SAS) AF: 0.454 AC: 2187 AN: 4820

European-Finnish (FIN) AF: 0.376 AC: 3965 AN: 10546

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.374 AC: 25436 AN: 67950

Other (OTH) AF: 0.498 AC: 1047 AN: 2102

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
PhyloP100		-1.8
Mutation Taster		=100/0	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: rs10512220; hg19: chr9-94806331;