14-77507442-T-G
Position:
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_004863.4(SPTLC2):c.*4842A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000335 in 152,134 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.00034 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
SPTLC2
NM_004863.4 3_prime_UTR
NM_004863.4 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.948
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BP6
Variant 14-77507442-T-G is Benign according to our data. Variant chr14-77507442-T-G is described in ClinVar as [Benign]. Clinvar id is 886802.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000335 (51/152134) while in subpopulation NFE AF= 0.000676 (46/68010). AF 95% confidence interval is 0.000521. There are 0 homozygotes in gnomad4. There are 19 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High AC in GnomAd4 at 51 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SPTLC2 | NM_004863.4 | c.*4842A>C | 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.*4842A>C | 3_prime_UTR_variant | 12/12 | 1 | NM_004863.4 | ENSP00000216484 | P1 | ||
SPTLC2 | ENST00000686627.1 | n.5563A>C | non_coding_transcript_exon_variant | 5/5 | ||||||
SPTLC2 | ENST00000687688.1 | n.6294A>C | non_coding_transcript_exon_variant | 9/9 | ||||||
SPTLC2 | ENST00000692906.1 | n.6263A>C | non_coding_transcript_exon_variant | 11/11 |
Frequencies
GnomAD3 genomes AF: 0.000335 AC: 51AN: 152018Hom.: 0 Cov.: 31
GnomAD3 genomes
AF:
AC:
51
AN:
152018
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 56Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 48
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
56
Hom.:
Cov.:
0
AF XY:
AC XY:
0
AN XY:
48
Gnomad4 AFR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.000335 AC: 51AN: 152134Hom.: 0 Cov.: 31 AF XY: 0.000256 AC XY: 19AN XY: 74356
GnomAD4 genome
AF:
AC:
51
AN:
152134
Hom.:
Cov.:
31
AF XY:
AC XY:
19
AN XY:
74356
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Neuropathy, hereditary sensory and autonomic, type 1C Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Mar 06, 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. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at