rs114519796

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_004863.4(SPTLC2):​c.723G>T​(p.Thr241Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0026 in 1,613,606 control chromosomes in the GnomAD database, including 113 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. T241T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.014 ( 66 hom., cov: 31)
Exomes 𝑓: 0.0014 ( 47 hom. )

Consequence

SPTLC2
NM_004863.4 synonymous

Scores

2

Clinical Significance

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

Conservation

PhyloP100: 2.28

Publications

1 publications found
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 Gene-Disease associations (from GenCC):
  • neuropathy, hereditary sensory and autonomic, type 1C
    Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Ambry Genetics
  • hereditary sensory and autonomic neuropathy type 1
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.21).
BP6
Variant 14-77570417-C-A is Benign according to our data. Variant chr14-77570417-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 314675.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=2.28 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0139 (2106/152032) while in subpopulation AFR AF = 0.0479 (1983/41442). AF 95% confidence interval is 0.0461. There are 66 homozygotes in GnomAd4. There are 1002 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
BS2
High AC in GnomAd4 at 2106 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SPTLC2NM_004863.4 linkc.723G>T p.Thr241Thr synonymous_variant Exon 5 of 12 ENST00000216484.7 NP_004854.1 O15270A0A024R6H1
SPTLC2XM_011537384.3 linkc.723G>T p.Thr241Thr synonymous_variant Exon 5 of 10 XP_011535686.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SPTLC2ENST00000216484.7 linkc.723G>T p.Thr241Thr synonymous_variant Exon 5 of 12 1 NM_004863.4 ENSP00000216484.2 O15270

Frequencies

GnomAD3 genomes
AF:
0.0138
AC:
2097
AN:
151914
Hom.:
65
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0478
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00552
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000622
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.0144
GnomAD2 exomes
AF:
0.00364
AC:
914
AN:
251318
AF XY:
0.00268
show subpopulations
Gnomad AFR exome
AF:
0.0489
Gnomad AMR exome
AF:
0.00278
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000123
Gnomad OTH exome
AF:
0.000489
GnomAD4 exome
AF:
0.00143
AC:
2092
AN:
1461574
Hom.:
47
Cov.:
32
AF XY:
0.00124
AC XY:
902
AN XY:
727102
show subpopulations
African (AFR)
AF:
0.0494
AC:
1654
AN:
33476
American (AMR)
AF:
0.00318
AC:
142
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26128
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39682
South Asian (SAS)
AF:
0.000174
AC:
15
AN:
86246
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53190
Middle Eastern (MID)
AF:
0.00416
AC:
24
AN:
5768
European-Non Finnish (NFE)
AF:
0.0000647
AC:
72
AN:
1111970
Other (OTH)
AF:
0.00306
AC:
185
AN:
60390
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.466
Heterozygous variant carriers
0
111
222
334
445
556
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
54
108
162
216
270
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0139
AC:
2106
AN:
152032
Hom.:
66
Cov.:
31
AF XY:
0.0135
AC XY:
1002
AN XY:
74304
show subpopulations
African (AFR)
AF:
0.0478
AC:
1983
AN:
41442
American (AMR)
AF:
0.00551
AC:
84
AN:
15250
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3468
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5166
South Asian (SAS)
AF:
0.000623
AC:
3
AN:
4818
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10580
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
290
European-Non Finnish (NFE)
AF:
0.0000882
AC:
6
AN:
68004
Other (OTH)
AF:
0.0143
AC:
30
AN:
2102
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
96
191
287
382
478
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
22
44
66
88
110
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.00420
Hom.:
9
Bravo
AF:
0.0162
EpiCase
AF:
0.000109
EpiControl
AF:
0.0000593

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
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. -

Jan 29, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Sep 21, 2023
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

not provided Benign:2
Mar 03, 2015
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

-
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
-0.21
CADD
Benign
8.1
DANN
Benign
0.58
PhyloP100
2.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Mutation Taster
=96/4
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

dbSNP: rs114519796; hg19: chr14-78036760; API