rs45461899

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_006415.4(SPTLC1):c.452G>T(p.Arg151Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0223 in 1,613,754 control chromosomes in the GnomAD database, including 468 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 35 hom., cov: 32)

Exomes 𝑓: 0.023 ( 433 hom. )

Consequence

SPTLC1
NM_006415.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 3.97

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 links:

SPTLC1 (HGNC:):

SPTLC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0135652125).

BP6

Variant 9-92068074-C-A is Benign according to our data. Variant chr9-92068074-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 367550.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-92068074-C-A is described in Lovd as [Benign]. Variant chr9-92068074-C-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0174 (2644/152248) while in subpopulation NFE AF= 0.0263 (1788/68020). AF 95% confidence interval is 0.0253. There are 35 homozygotes in gnomad4. There are 1232 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2644 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPTLC1	NM_006415.4 linkuse as main transcript	c.452G>T	p.Arg151Leu	missense_variant	6/15	ENST00000262554.7	NP_006406.1	O15269-1A0A024R277Q6NUL7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPTLC1	ENST00000262554.7 linkuse as main transcript	c.452G>T	p.Arg151Leu	missense_variant	6/15	1	NM_006415.4	ENSP00000262554.2		O15269-1

Frequencies

GnomAD3 genomes

AF:

0.0174

AC:

2644

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00449

Gnomad AMI

AF:

0.0164

Gnomad AMR

AF:

0.0135

Gnomad ASJ

AF:

0.0337

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0193

Gnomad FIN

AF:

0.0178

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0263

Gnomad OTH

AF:

0.0215

GnomAD3 exomes

AF:

0.0202

AC:

5073

AN:

250894

Hom.:

AF XY:

0.0213

AC XY:

2888

AN XY:

135624

show subpopulations

Gnomad AFR exome

AF:

0.00339

Gnomad AMR exome

AF:

0.0112

Gnomad ASJ exome

AF:

0.0309

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0164

Gnomad FIN exome

AF:

0.0185

Gnomad NFE exome

AF:

0.0286

Gnomad OTH exome

AF:

0.0289

GnomAD4 exome

AF:

0.0228

AC:

33384

AN:

1461506

Hom.:

433

Cov.:

AF XY:

0.0230

AC XY:

16693

AN XY:

727046

show subpopulations

Gnomad4 AFR exome

AF:

0.00278

Gnomad4 AMR exome

AF:

0.0118

Gnomad4 ASJ exome

AF:

0.0315

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.0178

Gnomad4 FIN exome

AF:

0.0200

Gnomad4 NFE exome

AF:

0.0250

Gnomad4 OTH exome

AF:

0.0224

GnomAD4 genome

AF:

0.0174

AC:

2644

AN:

152248

Hom.:

Cov.:

AF XY:

0.0166

AC XY:

1232

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.00448

Gnomad4 AMR

AF:

0.0135

Gnomad4 ASJ

AF:

0.0337

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0193

Gnomad4 FIN

AF:

0.0178

Gnomad4 NFE

AF:

0.0263

Gnomad4 OTH

AF:

0.0213

Alfa

AF:

0.0225

Hom.:

Bravo

AF:

0.0162

TwinsUK

AF:

0.0240

AC:

ALSPAC

AF:

0.0239

AC:

ESP6500AA

AF:

0.00409

AC:

ESP6500EA

AF:

0.0291

AC:

250

ExAC

AF:

0.0216

AC:

2621

Asia WGS

AF:

0.00664

AC:

AN:

3478

EpiCase

AF:

0.0274

EpiControl

AF:

0.0255

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Nov 21, 2023	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 09, 2023	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Charcot-Marie-Tooth disease

Benign:1

Benign, criteria provided, single submitter

clinical testing

Molecular Genetics Laboratory, London Health Sciences Centre

- -

Neuropathy, hereditary sensory and autonomic, type 1A

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Hereditary sensory and autonomic neuropathy type 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.57

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Uncertain

-0.070

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.76

Eigen

Benign

-0.0056

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.75

MetaRNN

Benign

0.014

MetaSVM

Uncertain

0.011

MutationAssessor

Benign

1.2

PrimateAI

Uncertain

0.54

PROVEAN

Pathogenic

-5.5

REVEL

Uncertain

0.48

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0040

Polyphen

0.013

Vest4

0.32

MPC

0.75

ClinPred

0.080

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.85

gMVP

0.91

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over