9-92080056-G-T

Variant names:

• chr9-92080056-G-T
• rs141265918
• NM_006415.4:c.387C>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_006415.4(SPTLC1):​c.387C>A​(p.Gly129Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G129G) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPTLC1 NM_006415.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP7: Synonymous conserved (PhyloP=-1.42 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006415.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPTLC1	NM_006415.4	MANE Select	c.387C>A	p.Gly129Gly	synonymous	Exon 5 of 15	NP_006406.1
	SPTLC1	NM_001281303.2		c.387C>A	p.Gly129Gly	synonymous	Exon 5 of 15	NP_001268232.1
	SPTLC1	NM_178324.3		c.387C>A	p.Gly129Gly	synonymous	Exon 5 of 6	NP_847894.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPTLC1	ENST00000262554.7	TSL:1 MANE Select	c.387C>A	p.Gly129Gly	synonymous	Exon 5 of 15	ENSP00000262554.2
	SPTLC1	ENST00000337841.4	TSL:1	c.387C>A	p.Gly129Gly	synonymous	Exon 5 of 6	ENSP00000337635.4
	SPTLC1	ENST00000686600.1		c.387C>A	p.Gly129Gly	synonymous	Exon 5 of 16	ENSP00000509268.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.21
DANN	Benign	0.56
PhyloP100		-1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs141265918; hg19: chr9-94842338;