22-30415957-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_012429.5(SEC14L2):c.781G>A(p.Gly261Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,870 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: not found (cov: 32)
Exomes 𝑓: 0.0000048 ( 0 hom. )
Consequence
SEC14L2
NM_012429.5 missense
NM_012429.5 missense
Scores
8
3
5
Clinical Significance
Conservation
PhyloP100: 9.46
Genes affected
SEC14L2 (HGNC:10699): (SEC14 like lipid binding 2) This gene encodes a cytosolic protein which belongs to a family of lipid-binding proteins including Sec14p, alpha-tocopherol transfer protein, and cellular retinol-binding protein. The encoded protein stimulates squalene monooxygenase which is a downstream enzyme in the cholesterol biosynthetic pathway. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Oct 2008]
RNF215 (HGNC:33434): (ring finger protein 215) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in Golgi to vacuole transport; protein targeting to vacuole; and ubiquitin-dependent protein catabolic process. Predicted to be integral component of membrane. Predicted to be part of Golgi transport complex. Predicted to be active in endosome; membrane; and trans-Golgi network. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.78
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SEC14L2 | NM_012429.5 | c.781G>A | p.Gly261Arg | missense_variant | 10/12 | ENST00000615189.5 | |
SEC14L2 | NM_033382.3 | c.781G>A | p.Gly261Arg | missense_variant | 10/11 | ||
SEC14L2 | NM_001291932.2 | c.619G>A | p.Gly207Arg | missense_variant | 9/11 | ||
SEC14L2 | NM_001204204.3 | c.532G>A | p.Gly178Arg | missense_variant | 8/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SEC14L2 | ENST00000615189.5 | c.781G>A | p.Gly261Arg | missense_variant | 10/12 | 1 | NM_012429.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251380Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135856
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GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461870Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 727228
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GnomAD4 genome ? Cov.: 32
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32
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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 | Sep 23, 2023 | The c.781G>A (p.G261R) alteration is located in exon 10 (coding exon 10) of the SEC14L2 gene. This alteration results from a G to A substitution at nucleotide position 781, causing the glycine (G) at amino acid position 261 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Uncertain
D;.;.;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
H;.;H;.;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
Sift4G
Uncertain
D;D;D;D;D
Polyphen
D;D;D;.;.
Vest4
MutPred
Gain of catalytic residue at G261 (P = 0.025);.;Gain of catalytic residue at G261 (P = 0.025);.;.;
MVP
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at