22-30409214-A-G

Variant summary

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

The NM_012429.5(SEC14L2):ā€‹c.451A>Gā€‹(p.Ile151Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000744 in 1,613,790 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000020 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000062 ( 0 hom. )

Consequence

SEC14L2
NM_012429.5 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.96
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]

Genome browser will be placed here

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=0.10978305).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SEC14L2NM_012429.5 linkuse as main transcriptc.451A>G p.Ile151Val missense_variant 6/12 ENST00000615189.5 NP_036561.1
SEC14L2NM_033382.3 linkuse as main transcriptc.451A>G p.Ile151Val missense_variant 6/11 NP_203740.1
SEC14L2NM_001291932.2 linkuse as main transcriptc.289A>G p.Ile97Val missense_variant 5/11 NP_001278861.1
SEC14L2NM_001204204.3 linkuse as main transcriptc.202A>G p.Ile68Val missense_variant 4/10 NP_001191133.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SEC14L2ENST00000615189.5 linkuse as main transcriptc.451A>G p.Ile151Val missense_variant 6/121 NM_012429.5 ENSP00000478755 P1O76054-1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152026
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000197
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000278
AC:
7
AN:
251430
Hom.:
0
AF XY:
0.0000368
AC XY:
5
AN XY:
135906
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000202
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000616
AC:
9
AN:
1461764
Hom.:
0
Cov.:
32
AF XY:
0.00000688
AC XY:
5
AN XY:
727178
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000179
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152026
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74248
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000197
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

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 GeneticsApr 12, 2022The c.451A>G (p.I151V) alteration is located in exon 6 (coding exon 6) of the SEC14L2 gene. This alteration results from a A to G substitution at nucleotide position 451, causing the isoleucine (I) at amino acid position 151 to be replaced by a valine (V). 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
0.093
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.34
CADD
Benign
19
DANN
Benign
0.81
DEOGEN2
Benign
0.061
T;T;.;.;.
Eigen
Benign
-0.96
Eigen_PC
Benign
-0.75
FATHMM_MKL
Uncertain
0.83
D
LIST_S2
Benign
0.55
T;T;T;T;T
M_CAP
Benign
0.025
T
MetaRNN
Benign
0.11
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.14
N;.;.;N;.
MutationTaster
Benign
0.80
N;N;N;N
PrimateAI
Benign
0.38
T
PROVEAN
Benign
-0.090
.;N;.;N;N
REVEL
Benign
0.15
Sift
Benign
0.22
.;T;.;T;T
Sift4G
Benign
1.0
T;T;T;T;T
Polyphen
0.0
B;.;B;B;.
Vest4
0.22
MutPred
0.48
Gain of sheet (P = 0.1451);.;.;Gain of sheet (P = 0.1451);.;
MVP
0.37
ClinPred
0.053
T
GERP RS
-0.052
Varity_R
0.21
gMVP
0.34

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1371975663; hg19: chr22-30805203; API