9-92031163-A-C

Position:

• chr9-92031163-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_006415.4(SPTLC1):​c.*1302T>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 0.107 in 152,638 control chromosomes in the GnomAD database, including 1,879 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (1879 hom., cov: 32)
  • Exomes 𝑓: 0.012 (0 hom.)
• Consequence: SPTLC1 NM_006415.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.75

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.23).
• BP6: Variant 9-92031163-A-C is Benign according to our data. Variant chr9-92031163-A-C is described in ClinVar as [Benign]. Clinvar id is 367526.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPTLC1	NM_006415.4	c.*1302T>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	c.*1302T>G		3_prime_UTR_variant	15/15	1	NM_006415.4	ENSP00000262554	P1

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16285 AN: 152092 Hom.: 1874 Cov.: 32

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0551

Gnomad ASJ AF: 0.0531

Gnomad EAS AF: 0.0323

Gnomad SAS AF: 0.0617

Gnomad FIN AF: 0.0251

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0309

Gnomad OTH AF: 0.0816

GnomAD4 exome AF: 0.0117 AC: 5 AN: 428 Hom.: 0 Cov.: 0 AF XY: 0.00781 AC XY: 2 AN XY: 256

Gnomad4 FIN exome AF: 0.0118

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.107 AC: 16311 AN: 152210 Hom.: 1879 Cov.: 32 AF XY: 0.104 AC XY: 7747 AN XY: 74412

Gnomad4 AFR AF: 0.295

Gnomad4 AMR AF: 0.0549

Gnomad4 ASJ AF: 0.0531

Gnomad4 EAS AF: 0.0323

Gnomad4 SAS AF: 0.0611

Gnomad4 FIN AF: 0.0251

Gnomad4 NFE AF: 0.0309

Gnomad4 OTH AF: 0.0807

Alfa AF: 0.0605 Hom.: 173

Bravo AF: 0.117

Asia WGS AF: 0.0710 AC: 246 AN: 3460

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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

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	-0.23
CADD	Benign	19
DANN	Benign	0.87

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7035964; hg19: chr9-94793445; COSMIC: COSV52768218;