NM_006415.4(SPTLC1):c.112CTT[1] (p.Leu39del) AND Hereditary sensory and autonomic neuropathy type 1

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 24, 2021
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001858688.5

Allele description [Variation Report for NM_006415.4(SPTLC1):c.112CTT[1] (p.Leu39del)]

NM_006415.4(SPTLC1):c.112CTT[1] (p.Leu39del)

Gene:

SPTLC1:serine palmitoyltransferase long chain base subunit 1 [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

9q22.31

Genomic location:

Preferred name:

NM_006415.4(SPTLC1):c.112CTT[1] (p.Leu39del)

HGVS:

NC_000009.12:g.92112503AAG[1]
NC_000009.12:g.92112503_92112505AAG[1]
NG_007950.1:g.7901CTT[1]
NM_001281303.2:c.112CTT[1]
NM_001368272.1:c.-388CTT[1]
NM_001368273.1:c.-354CTT[1]
NM_006415.4:c.112CTT[1]MANE SELECT
NM_178324.3:c.112CTT[1]
NP_001268232.1:p.Leu39del
NP_006406.1:p.Leu39del
NP_847894.1:p.Leu39del
LRG_272t1:c.115_117del
LRG_272:g.7901CTT[1]
NC_000009.11:g.94874785AAG[1]
NC_000009.11:g.94874785_94874787del
NC_000009.11:g.94874785_94874787delAAG
NM_006415.2:c.115_117delCTT
NM_006415.4:c.115_117delMANE SELECT
NM_006415.4:c.115_117delCTTMANE SELECT

Protein change:

L39del

Links:

OMIM: 605712.0010; dbSNP: rs1197928094

NCBI 1000 Genomes Browser:

rs1197928094

Molecular consequence:

NM_001368272.1:c.-388CTT[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001368273.1:c.-354CTT[1] - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001281303.2:c.112CTT[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_006415.4:c.112CTT[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_178324.3:c.112CTT[1] - inframe_deletion - [Sequence Ontology: SO:0001822]

Condition(s)

Name:: Hereditary sensory and autonomic neuropathy type 1 (HSAN1)
Synonyms:: HSAN 1; Neuropathy hereditary sensory radicular, autosomal dominant; Hereditary sensory neuropathy type 1; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0018213; MedGen: C0020071; Orphanet: 36386

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002213359	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 24, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 34059824, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002213359

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 24, 2021)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Childhood amyotrophic lateral sclerosis caused by excess sphingolipid synthesis.

Mohassel P, Donkervoort S, Lone MA, Nalls M, Gable K, Gupta SD, Foley AR, Hu Y, Saute JAM, Moreira AL, Kok F, Introna A, Logroscino G, Grunseich C, Nickolls AR, Pourshafie N, Neuhaus SB, Saade D, Gangfuß A, Kölbel H, Piccus Z, Le Pichon CE, et al.

Nat Med. 2021 Jul;27(7):1197-1204. doi: 10.1038/s41591-021-01346-1. Epub 2021 May 31.

PubMed [citation]

PMID:: 34059824
PMCID:: PMC9309980

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9..

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002213359.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This variant, c.115_117del, results in the deletion of 1 amino acid(s) of the SPTLC1 protein (p.Leu39del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with juvenile ALS (PMID: 34059824; Invitae). In at least one individual the variant was observed to be de novo. It has also been observed to segregate with disease in related individuals. Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this variant affects SPTLC1 function (PMID: 34059824). For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Feb 25, 2025

ClinVar

Relating variation to medicine