rs119482084

Positions:

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PP3BP6_Very_StrongBS1BS2

The NM_006415.4(SPTLC1):c.1160G>C(p.Gly387Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000557 in 1,613,624 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00057 ( 0 hom. )

Consequence

SPTLC1
NM_006415.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts U:2B:7O:1

Conservation

PhyloP100: 6.89

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 -15 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.833

BP6

Variant 9-92038342-C-G is Benign according to our data. Variant chr9-92038342-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 4802.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-92038342-C-G is described in Lovd as [Benign]. Variant chr9-92038342-C-G is described in Lovd as [Pathogenic]. Variant chr9-92038342-C-G is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000388 (59/152234) while in subpopulation AMR AF= 0.000784 (12/15302). AF 95% confidence interval is 0.000452. There are 0 homozygotes in gnomad4. There are 25 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 59 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPTLC1	NM_006415.4 linkuse as main transcript	c.1160G>C	p.Gly387Ala	missense_variant	13/15	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.1160G>C	p.Gly387Ala	missense_variant	13/15	1	NM_006415.4	ENSP00000262554.2		O15269-1

Frequencies

GnomAD3 genomes

AF:

0.000388

AC:

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000967

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000573

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000429

AC:

108

AN:

251488

Hom.:

AF XY:

0.000331

AC XY:

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000723

Gnomad ASJ exome

AF:

0.000198

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000633

Gnomad OTH exome

AF:

0.000651

GnomAD4 exome

AF:

0.000574

AC:

839

AN:

1461390

Hom.:

Cov.:

AF XY:

0.000575

AC XY:

418

AN XY:

727054

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000671

Gnomad4 ASJ exome

AF:

0.000191

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.000672

Gnomad4 OTH exome

AF:

0.000596

GnomAD4 genome

AF:

0.000388

AC:

AN:

152234

Hom.:

Cov.:

AF XY:

0.000336

AC XY:

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.0000964

Gnomad4 AMR

AF:

0.000784

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000623

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000573

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000681

Hom.:

Bravo

AF:

0.000397

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000379

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000763

EpiControl

AF:

0.000711

ClinVar

Significance: Benign/Likely benign

Submissions summary: Uncertain:2Benign:7Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Neuropathy, hereditary sensory and autonomic, type 1A

Benign:2Other:1

Likely benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -
not provided, no classification provided	literature only	GeneReviews	-	- -
Likely benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Feb 03, 2020	- -

Charcot-Marie-Tooth disease

Uncertain:1Benign:1

Uncertain significance, no assertion criteria provided	literature only	Inherited Neuropathy Consortium	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Molecular Genetics Laboratory, London Health Sciences Centre	-	- -

Hereditary sensory and autonomic neuropathy type 1

Uncertain:1Benign:1

Uncertain significance, no assertion criteria provided	literature only	OMIM	Apr 01, 2009	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 20, 2024	- -

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2023	SPTLC1: BS3:Supporting, BS2 -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 06, 2019	This variant is associated with the following publications: (PMID: 19132419, 21618344, 15037712, 19651702) -

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 18, 2019

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Uncertain

0.092

BayesDel_noAF

Pathogenic

0.27

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.77

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.93

M_CAP

Uncertain

0.24

MetaRNN

Pathogenic

0.83

MetaSVM

Pathogenic

0.81

MutationAssessor

Uncertain

2.8

PrimateAI

Benign

0.48

PROVEAN

Uncertain

-3.1

REVEL

Pathogenic

0.81

Sift

Uncertain

0.013

Sift4G

Uncertain

0.032

Polyphen

0.41

Vest4

0.92

MVP

0.89

MPC

1.1

ClinPred

0.25

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.43

gMVP

0.80

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