chr9-92060258-G-A

Variant names:

• chr9-92060258-G-A
• rs7872515
• NM_006415.4:c.561-950C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006415.4(SPTLC1):​c.561-950C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 151,976 control chromosomes in the GnomAD database, including 6,701 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 0.25 (6701 hom., cov: 32)
• Consequence: SPTLC1 NM_006415.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00700
• Publications: 11 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPTLC1	NM_006415.4	c.561-950C>T		intron_variant	Intron 6 of 14	ENST00000262554.7	NP_006406.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPTLC1	ENST00000262554.7	c.561-950C>T		intron_variant	Intron 6 of 14	1	NM_006415.4	ENSP00000262554.2

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37792 AN: 151858 Hom.: 6686 Cov.: 32

Gnomad AFR AF: 0.494

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.229

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.218

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

GnomAD4 genome AF: 0.249 AC: 37845 AN: 151976 Hom.: 6701 Cov.: 32 AF XY: 0.251 AC XY: 18623 AN XY: 74302

African (AFR) AF: 0.494 AC: 20445 AN: 41408

American (AMR) AF: 0.275 AC: 4200 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 741 AN: 3470

East Asian (EAS) AF: 0.305 AC: 1573 AN: 5158

South Asian (SAS) AF: 0.149 AC: 720 AN: 4818

European-Finnish (FIN) AF: 0.177 AC: 1872 AN: 10558

Middle Eastern (MID) AF: 0.216 AC: 63 AN: 292

European-Non Finnish (NFE) AF: 0.113 AC: 7682 AN: 67980

Other (OTH) AF: 0.218 AC: 460 AN: 2110

Alfa AF: 0.166 Hom.: 8739

Bravo AF: 0.268

Asia WGS AF: 0.257 AC: 893 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.4
DANN	Benign	0.30
PhyloP100		-0.0070
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: rs7872515; hg19: chr9-94822540;