9-92032020-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006415.4(SPTLC1):c.*445A>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 0.0535 in 402,286 control chromosomes in the GnomAD database, including 715 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.052 (264 hom., cov: 32)
  • Exomes 𝑓: 0.055 (451 hom.)
• Consequence: SPTLC1 NM_006415.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.33

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 9-92032020-T-C is Benign according to our data. Variant chr9-92032020-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 367538.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPTLC1	NM_006415.4	c.*445A>G		3_prime_UTR_variant	15/15	ENST00000262554.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPTLC1	ENST00000262554.7	c.*445A>G		3_prime_UTR_variant	15/15	1	NM_006415.4	P1

Frequencies

GnomAD3 genomes AF: 0.0519 AC: 7892 AN: 152156 Hom.: 264 Cov.: 32

Gnomad AFR AF: 0.0324

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.0470

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0118

Gnomad FIN AF: 0.0862

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0613

Gnomad OTH AF: 0.0612

GnomAD4 exome AF: 0.0545 AC: 13630 AN: 250012 Hom.: 451 Cov.: 2 AF XY: 0.0542 AC XY: 6906 AN XY: 127502

Gnomad4 AFR exome AF: 0.0309

Gnomad4 AMR exome AF: 0.0443

Gnomad4 ASJ exome AF: 0.122

Gnomad4 EAS exome AF: 0.0000950

Gnomad4 SAS exome AF: 0.0142

Gnomad4 FIN exome AF: 0.0836

Gnomad4 NFE exome AF: 0.0593

Gnomad4 OTH exome AF: 0.0590

GnomAD4 genome AF: 0.0519 AC: 7903 AN: 152274 Hom.: 264 Cov.: 32 AF XY: 0.0517 AC XY: 3852 AN XY: 74466

Gnomad4 AFR AF: 0.0326

Gnomad4 AMR AF: 0.0469

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.000385

Gnomad4 SAS AF: 0.0118

Gnomad4 FIN AF: 0.0862

Gnomad4 NFE AF: 0.0613

Gnomad4 OTH AF: 0.0605

Alfa AF: 0.0617 Hom.: 294

Bravo AF: 0.0487

Asia WGS AF: 0.0120 AC: 43 AN: 3474

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Neuropathy, hereditary sensory and autonomic, type 1A Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.20
Dann	Benign	0.43

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

Other links and lift over

dbSNP: rs7944; hg19: chr9-94794302;