chr20-13160040-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_018327.4(SPTLC3):c.1453G>A(p.Val485Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000744 in 1,613,202 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000048 ( 0 hom. )
Consequence
SPTLC3
NM_018327.4 missense
NM_018327.4 missense
Scores
10
6
3
Clinical Significance
Conservation
PhyloP100: 6.37
Genes affected
SPTLC3 (HGNC:16253): (serine palmitoyltransferase long chain base subunit 3) This gene encodes a subunit of the serine palmitoyltransferase complex which catalyzes the rate-limiting step in sphingolipid biosynthesis. This subunit metabolizes lauroyl- and myristoyl-CoA and generates C14 and C16-sphingoid bases. [provided by RefSeq, Mar 2017]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.911
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SPTLC3 | NM_018327.4 | c.1453G>A | p.Val485Met | missense_variant | 11/12 | ENST00000399002.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SPTLC3 | ENST00000399002.7 | c.1453G>A | p.Val485Met | missense_variant | 11/12 | 1 | NM_018327.4 | P1 | |
SPTLC3 | ENST00000431275.1 | c.247G>A | p.Val83Met | missense_variant | 3/4 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000330 AC: 5AN: 151520Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249164Hom.: 0 AF XY: 0.00000740 AC XY: 1AN XY: 135160
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GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461682Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 727144
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GnomAD4 genome ? AF: 0.0000330 AC: 5AN: 151520Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 73936
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 17, 2023 | The c.1453G>A (p.V485M) alteration is located in exon 11 (coding exon 11) of the SPTLC3 gene. This alteration results from a G to A substitution at nucleotide position 1453, causing the valine (V) at amino acid position 485 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Uncertain
D
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
H
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Pathogenic
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Loss of catalytic residue at V485 (P = 0.0712);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at