chr9-92038375-G-C

Variant names:

• chr9-92038375-G-C
• rs1357342455
• NM_006415.4:c.1137-10C>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_006415.4(SPTLC1):​c.1137-10C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 151,424 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.000013 (0 hom., cov: 33)
• Consequence: SPTLC1 NM_006415.4 intron
• Scores: Splicing: ADA: 0.004303
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.353
• 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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 9-92038375-G-C is Benign according to our data. Variant chr9-92038375-G-C is described in CliVar as Likely_benign. Clinvar id is 456601.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-92038375-G-C is described in CliVar as Likely_benign. Clinvar id is 456601.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-92038375-G-C is described in CliVar as Likely_benign. Clinvar id is 456601.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-92038375-G-C is described in CliVar as Likely_benign. Clinvar id is 456601.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-92038375-G-C is described in CliVar as Likely_benign. Clinvar id is 456601.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-92038375-G-C is described in CliVar as Likely_benign. Clinvar id is 456601.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-92038375-G-C is described in CliVar as Likely_benign. Clinvar id is 456601.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-92038375-G-C is described in CliVar as Likely_benign. Clinvar id is 456601.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-92038375-G-C is described in CliVar as Likely_benign. Clinvar id is 456601.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-92038375-G-C is described in CliVar as Likely_benign. Clinvar id is 456601.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-92038375-G-C is described in CliVar as Likely_benign. Clinvar id is 456601.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-92038375-G-C is described in CliVar as Likely_benign. Clinvar id is 456601.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-92038375-G-C is described in CliVar as Likely_benign. Clinvar id is 456601.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-92038375-G-C is described in CliVar as Likely_benign. Clinvar id is 456601.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-92038375-G-C is described in CliVar as Likely_benign. Clinvar id is 456601.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-92038375-G-C is described in CliVar as Likely_benign. Clinvar id is 456601.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-92038375-G-C is described in CliVar as Likely_benign. Clinvar id is 456601.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-92038375-G-C is described in CliVar as Likely_benign. Clinvar id is 456601.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-92038375-G-C is described in CliVar as Likely_benign. Clinvar id is 456601.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-92038375-G-C is described in CliVar as Likely_benign. Clinvar id is 456601.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-92038375-G-C is described in CliVar as Likely_benign. Clinvar id is 456601.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-92038375-G-C is described in CliVar as Likely_benign. Clinvar id is 456601.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-92038375-G-C is described in CliVar as Likely_benign. Clinvar id is 456601.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPTLC1	NM_006415.4	c.1137-10C>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.1137-10C>G		intron_variant	Intron 12 of 14	1	NM_006415.4	ENSP00000262554.2

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151424 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 23

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151424 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74000

African (AFR) AF: 0.00 AC: 0 AN: 40722

American (AMR) AF: 0.00 AC: 0 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2080

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hereditary sensory and autonomic neuropathy type 1 Benign:1

Mar 12, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	13
DANN	Benign	0.67
PhyloP100		0.35
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0043
dbscSNV1_RF	Benign	0.12
SpliceAI score (max)		0.010		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: rs1357342455; hg19: chr9-94800657;