14-77506204-G-C

Position:

• chr14-77506204-G-C

Variant summary

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

The ENST00000216484.7(SPTLC2):​c.*6080C>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 0.0506 in 152,268 control chromosomes in the GnomAD database, including 382 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.051 (382 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SPTLC2 ENST00000216484.7 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0780

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=-0.84).
• BP6: Variant 14-77506204-G-C is Benign according to our data. Variant chr14-77506204-G-C is described in ClinVar as [Benign]. Clinvar id is 314571.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPTLC2	NM_004863.4	c.*6080C>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.*6080C>G		3_prime_UTR_variant	12/12	1	NM_004863.4	ENSP00000216484	P1
SPTLC2	ENST00000686627.1	n.6801C>G		non_coding_transcript_exon_variant	5/5
SPTLC2	ENST00000687688.1	n.7532C>G		non_coding_transcript_exon_variant	9/9
SPTLC2	ENST00000692906.1	n.7501C>G		non_coding_transcript_exon_variant	11/11

Frequencies

GnomAD3 genomes AF: 0.0505 AC: 7684 AN: 152150 Hom.: 381 Cov.: 32

Gnomad AFR AF: 0.0130

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.0202

Gnomad EAS AF: 0.00366

Gnomad SAS AF: 0.0421

Gnomad FIN AF: 0.0244

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0617

Gnomad OTH AF: 0.0411

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 12 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 12

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0506 AC: 7698 AN: 152268 Hom.: 382 Cov.: 32 AF XY: 0.0493 AC XY: 3673 AN XY: 74448

Gnomad4 AFR AF: 0.0130

Gnomad4 AMR AF: 0.149

Gnomad4 ASJ AF: 0.0202

Gnomad4 EAS AF: 0.00366

Gnomad4 SAS AF: 0.0422

Gnomad4 FIN AF: 0.0244

Gnomad4 NFE AF: 0.0617

Gnomad4 OTH AF: 0.0407

Alfa AF: 0.0501 Hom.: 23

Bravo AF: 0.0585

Asia WGS AF: 0.0220 AC: 75 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 12, 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	-0.84
CADD	Benign	0.56
DANN	Benign	0.36

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: rs56040359; hg19: chr14-77972547;