rs7856177

Positions:

• chr9-92077060-A-G
• chr9-92077060-A-T

Variant summary

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

The NM_006415.4(SPTLC1):​c.427+2956T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 151,886 control chromosomes in the GnomAD database, including 11,773 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 0.33 (11768 hom., cov: 31)
  • Exomes 𝑓: 0.24 (5 hom.)
• Consequence: SPTLC1 NM_006415.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13

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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPTLC1	NM_006415.4	c.427+2956T>C		intron_variant		ENST00000262554.7	NP_006406.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPTLC1	ENST00000262554.7	c.427+2956T>C		intron_variant		1	NM_006415.4	ENSP00000262554	P1

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49787 AN: 151696 Hom.: 11732 Cov.: 31

Gnomad AFR AF: 0.659

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.295

GnomAD4 exome AF: 0.243 AC: 17 AN: 70 Hom.: 5 Cov.: 0 AF XY: 0.180 AC XY: 9 AN XY: 50

Gnomad4 AFR exome AF: 1.00

Gnomad4 ASJ exome AF: 1.00

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.104

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.329 AC: 49882 AN: 151816 Hom.: 11768 Cov.: 31 AF XY: 0.329 AC XY: 24424 AN XY: 74200

Gnomad4 AFR AF: 0.659

Gnomad4 AMR AF: 0.330

Gnomad4 ASJ AF: 0.278

Gnomad4 EAS AF: 0.367

Gnomad4 SAS AF: 0.263

Gnomad4 FIN AF: 0.192

Gnomad4 NFE AF: 0.157

Gnomad4 OTH AF: 0.301

Alfa AF: 0.204 Hom.: 1924

Bravo AF: 0.353

Asia WGS AF: 0.357 AC: 1243 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.36

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: rs7856177; hg19: chr9-94839342;