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GeneBe

22-30407128-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_012429.5(SEC14L2):c.208A>G(p.Asn70Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

SEC14L2
NM_012429.5 missense

Scores

3
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.41
Variant links:
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.24474505).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SEC14L2NM_012429.5 linkuse as main transcriptc.208A>G p.Asn70Asp missense_variant 4/12 ENST00000615189.5
SEC14L2NM_033382.3 linkuse as main transcriptc.208A>G p.Asn70Asp missense_variant 4/11
SEC14L2NM_001291932.2 linkuse as main transcriptc.46A>G p.Asn16Asp missense_variant 3/11
SEC14L2NM_001204204.3 linkuse as main transcriptc.174+743A>G intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SEC14L2ENST00000615189.5 linkuse as main transcriptc.208A>G p.Asn70Asp missense_variant 4/121 NM_012429.5 P1O76054-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

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 submitterclinical testingAmbry GeneticsJan 09, 2024The c.208A>G (p.N70D) alteration is located in exon 4 (coding exon 4) of the SEC14L2 gene. This alteration results from a A to G substitution at nucleotide position 208, causing the asparagine (N) at amino acid position 70 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.098
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.48
Cadd
Benign
21
Dann
Uncertain
0.99
DEOGEN2
Benign
0.31
T;T;.;.;T
Eigen
Benign
-0.32
Eigen_PC
Benign
-0.17
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.91
D;D;D;D;D
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.24
T;T;T;T;T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
1.7
L;.;L;.;.
MutationTaster
Benign
0.88
D;D;D;D
PrimateAI
Benign
0.44
T
Sift4G
Benign
0.47
T;T;T;T;T
Polyphen
0.0
B;.;B;.;.
Vest4
0.29
MutPred
0.37
Gain of ubiquitination at K66 (P = 0.0645);.;Gain of ubiquitination at K66 (P = 0.0645);.;.;
MVP
0.73
ClinPred
0.51
D
GERP RS
3.6
Varity_R
0.17
gMVP
0.46

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-30803117; API