Variant chr9-92032341-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_006415.4(SPTLC1):c.*124A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00691 in 1,563,130 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0062 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0070 ( 36 hom. )

Consequence

SPTLC1
NM_006415.4 3_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.874

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:

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 (BayesDel_noAF=-0.9).

BP6

Variant 9-92032341-T-C is Benign according to our data. Variant chr9-92032341-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 367542.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-92032341-T-C is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00622 (948/152310) while in subpopulation NFE AF= 0.00783 (533/68038). AF 95% confidence interval is 0.00728. There are 6 homozygotes in gnomad4. There are 465 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 948 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPTLC1	NM_006415.4 linkuse as main transcript	c.*124A>G		3_prime_UTR_variant	15/15	ENST00000262554.7	NP_006406.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPTLC1	ENST00000262554.7 linkuse as main transcript	c.*124A>G		3_prime_UTR_variant	15/15	1	NM_006415.4	ENSP00000262554	P1	O15269-1

Frequencies

GnomAD3 genomes

AF:

0.00622

AC:

947

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00379

Gnomad AMI

AF:

0.0559

Gnomad AMR

AF:

0.00589

Gnomad ASJ

AF:

0.00289

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00867

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00783

Gnomad OTH

AF:

0.00622

GnomAD3 exomes

AF:

0.00477

AC:

847

AN:

177666

Hom.:

AF XY:

0.00473

AC XY:

452

AN XY:

95476

show subpopulations

Gnomad AFR exome

AF:

0.00272

Gnomad AMR exome

AF:

0.00225

Gnomad ASJ exome

AF:

0.00181

Gnomad EAS exome

AF:

0.0000770

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00909

Gnomad NFE exome

AF:

0.00801

Gnomad OTH exome

AF:

0.00470

GnomAD4 exome

AF:

0.00698

AC:

9848

AN:

1410820

Hom.:

Cov.:

AF XY:

0.00681

AC XY:

4760

AN XY:

698556

show subpopulations

Gnomad4 AFR exome

AF:

0.00320

Gnomad4 AMR exome

AF:

0.00254

Gnomad4 ASJ exome

AF:

0.00288

Gnomad4 EAS exome

AF:

0.0000271

Gnomad4 SAS exome

AF:

0.0000122

Gnomad4 FIN exome

AF:

0.00942

Gnomad4 NFE exome

AF:

0.00807

Gnomad4 OTH exome

AF:

0.00640

GnomAD4 genome

AF:

0.00622

AC:

948

AN:

152310

Hom.:

Cov.:

AF XY:

0.00624

AC XY:

465

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00380

Gnomad4 AMR

AF:

0.00588

Gnomad4 ASJ

AF:

0.00289

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00867

Gnomad4 NFE

AF:

0.00783

Gnomad4 OTH

AF:

0.00616

Alfa

AF:

0.00454

Hom.:

Bravo

AF:

0.00635

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 22, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	May 01, 2023	SPTLC1: BS2 -

Neuropathy, hereditary sensory and autonomic, type 1A

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.41

DANN

Benign

0.53

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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