chr14-77597351-T-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_004863.4(SPTLC2):c.162A>C(p.Leu54Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00185 in 1,614,158 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0096 ( 22 hom., cov: 33)

Exomes 𝑓: 0.0010 ( 26 hom. )

Consequence

SPTLC2
NM_004863.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.560

Variant links:

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]

SPTLC2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 14-77597351-T-G is Benign according to our data. Variant chr14-77597351-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 314680.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-77597351-T-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.56 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00961 (1464/152346) while in subpopulation AFR AF= 0.0336 (1396/41578). AF 95% confidence interval is 0.0321. There are 22 homozygotes in gnomad4. There are 711 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1464 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPTLC2	NM_004863.4 link	c.162A>C	p.Leu54Leu	synonymous_variant	Exon 2 of 12	ENST00000216484.7	NP_004854.1	O15270A0A024R6H1
SPTLC2	XM_011537384.3 link	c.162A>C	p.Leu54Leu	synonymous_variant	Exon 2 of 10		XP_011535686.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SPTLC2	ENST00000216484.7 link	c.162A>C	p.Leu54Leu	synonymous_variant	Exon 2 of 12	1	NM_004863.4	ENSP00000216484.2	O15270
SPTLC2	ENST00000557566.1 link	n.1A>C		non_coding_transcript_exon_variant	Exon 1 of 2	2
SPTLC2	ENST00000554901.1 link	c.-31A>C		upstream_gene_variant		1		ENSP00000452189.1	H0YJV2

Frequencies

GnomAD3 genomes

AF:

0.00962

AC:

1465

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0337

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00268

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00955

GnomAD3 exomes

AF:

0.00261

AC:

655

AN:

251426

Hom.:

AF XY:

0.00210

AC XY:

285

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.0351

Gnomad AMR exome

AF:

0.00165

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000158

Gnomad OTH exome

AF:

0.00130

GnomAD4 exome

AF:

0.00104

AC:

1521

AN:

1461812

Hom.:

Cov.:

AF XY:

0.000924

AC XY:

672

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.0348

Gnomad4 AMR exome

AF:

0.00179

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000120

Gnomad4 OTH exome

AF:

0.00224

GnomAD4 genome

AF:

0.00961

AC:

1464

AN:

152346

Hom.:

Cov.:

AF XY:

0.00954

AC XY:

711

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.0336

Gnomad4 AMR

AF:

0.00268

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00945

Alfa

AF:

0.00348

Hom.:

Bravo

AF:

0.0117

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000178

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Neuropathy, hereditary sensory and autonomic, type 1C

Benign:4

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 08, 2021

Fulgent Genetics, Fulgent Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Nov 06, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Aug 05, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

1.1

DANN

Benign

0.67

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