rs2297568

Variant names:

• chr9-92112369-G-A
• rs2297568
• NM_006415.4:c.165+86C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-92112369-G-A
• chr9-92112369-G-C
• chr9-92112369-G-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.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
• Publications: 5 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=-0.77).
• 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 rank	MANE	Protein	UniProt
SPTLC1	NM_006415.4	c.165+86C>T		intron_variant	Intron 2 of 14	ENST00000262554.7	NP_006406.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPTLC1	ENST00000262554.7	c.165+86C>T		intron_variant	Intron 2 of 14	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

African (AFR) AF: 0.855 AC: 17699 AN: 20694

American (AMR) AF: 0.586 AC: 22327 AN: 38078

Ashkenazi Jewish (ASJ) AF: 0.515 AC: 11008 AN: 21370

East Asian (EAS) AF: 0.408 AC: 14644 AN: 35910

South Asian (SAS) AF: 0.456 AC: 31838 AN: 69876

European-Finnish (FIN) AF: 0.377 AC: 17766 AN: 47076

Middle Eastern (MID) AF: 0.469 AC: 1326 AN: 2830

European-Non Finnish (NFE) AF: 0.375 AC: 198564 AN: 529126

Other (OTH) AF: 0.440 AC: 16905 AN: 38384

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

African (AFR) AF: 0.846 AC: 35092 AN: 41502

American (AMR) AF: 0.567 AC: 8675 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.515 AC: 1787 AN: 3472

East Asian (EAS) AF: 0.433 AC: 2244 AN: 5178

South Asian (SAS) AF: 0.451 AC: 2173 AN: 4816

European-Finnish (FIN) AF: 0.371 AC: 3903 AN: 10512

Middle Eastern (MID) AF: 0.531 AC: 155 AN: 292

European-Non Finnish (NFE) AF: 0.371 AC: 25249 AN: 67966

Other (OTH) AF: 0.494 AC: 1043 AN: 2110

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
PhyloP100		0.82
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: rs2297568; hg19: chr9-94874651;