14-77506753-T-C

Position:

• chr14-77506753-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004863.4(SPTLC2):​c.*5531A>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 0.0591 in 152,250 control chromosomes in the GnomAD database, including 292 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.059 (292 hom., cov: 32)
  • Exomes 𝑓: 0.056 (0 hom.)
• Consequence: SPTLC2 NM_004863.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.35

Genes affected

SPTLC2 (HGNC:11278): (serine palmitoyltransferase long chain base subunit 2) This gene encodes a long chain base subunit of serine palmitoyltransferase. Serine palmitoyltransferase, which consists of two different subunits, is the key enzyme in sphingolipid biosynthesis. It catalyzes the pyridoxal-5-prime-phosphate-dependent condensation of L-serine and palmitoyl-CoA to 3-oxosphinganine. Mutations in this gene were identified in patients with hereditary sensory neuropathy type I. [provided by RefSeq, Mar 2011]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 14-77506753-T-C is Benign according to our data. Variant chr14-77506753-T-C is described in ClinVar as [Benign]. Clinvar id is 314575.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.083 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPTLC2	NM_004863.4	c.*5531A>G		3_prime_UTR_variant	12/12	ENST00000216484.7	NP_004854.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPTLC2	ENST00000216484.7	c.*5531A>G		3_prime_UTR_variant	12/12	1	NM_004863.4	ENSP00000216484	P1
SPTLC2	ENST00000686627.1	n.6252A>G		non_coding_transcript_exon_variant	5/5
SPTLC2	ENST00000687688.1	n.6983A>G		non_coding_transcript_exon_variant	9/9
SPTLC2	ENST00000692906.1	n.6952A>G		non_coding_transcript_exon_variant	11/11

Frequencies

GnomAD3 genomes AF: 0.0592 AC: 9002 AN: 152114 Hom.: 292 Cov.: 32

Gnomad AFR AF: 0.0855

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0401

Gnomad ASJ AF: 0.0746

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0381

Gnomad FIN AF: 0.0633

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0527

Gnomad OTH AF: 0.0592

GnomAD4 exome AF: 0.0556 AC: 1 AN: 18 Hom.: 0 Cov.: 0 AF XY: 0.0714 AC XY: 1 AN XY: 14

Gnomad4 AFR exome AF: 0.500

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0591 AC: 9003 AN: 152232 Hom.: 292 Cov.: 32 AF XY: 0.0589 AC XY: 4386 AN XY: 74430

Gnomad4 AFR AF: 0.0853

Gnomad4 AMR AF: 0.0401

Gnomad4 ASJ AF: 0.0746

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0382

Gnomad4 FIN AF: 0.0633

Gnomad4 NFE AF: 0.0527

Gnomad4 OTH AF: 0.0586

Alfa AF: 0.0543 Hom.: 289

Bravo AF: 0.0585

Asia WGS AF: 0.0200 AC: 71 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.099
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

Other links and lift over

dbSNP: rs17105886; hg19: chr14-77973096;