9-92038375-G-C

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_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

Variant links:

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

SPTLC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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 link	c.1137-10C>G		intron_variant	Intron 12 of 14	ENST00000262554.7	NP_006406.1	O15269-1A0A024R277Q6NUL7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPTLC1	ENST00000262554.7 link	c.1137-10C>G		intron_variant	Intron 12 of 14	1	NM_006415.4	ENSP00000262554.2		O15269-1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151424

Hom.:

Cov.:

show subpopulations

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.:

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151424

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74000

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40722

American (AMR)

AF:

0.00

AC:

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

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

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over