22-30415803-G-A

Variant summary

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

The NM_012429.5(SEC14L2):​c.709G>A​(p.Val237Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000186 in 1,614,026 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

SEC14L2
NM_012429.5 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.133
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=0.11099824).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SEC14L2NM_012429.5 linkuse as main transcriptc.709G>A p.Val237Met missense_variant 9/12 ENST00000615189.5
SEC14L2NM_033382.3 linkuse as main transcriptc.709G>A p.Val237Met missense_variant 9/11
SEC14L2NM_001291932.2 linkuse as main transcriptc.547G>A p.Val183Met missense_variant 8/11
SEC14L2NM_001204204.3 linkuse as main transcriptc.460G>A p.Val154Met missense_variant 7/10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SEC14L2ENST00000615189.5 linkuse as main transcriptc.709G>A p.Val237Met missense_variant 9/121 NM_012429.5 P1O76054-1

Frequencies

GnomAD3 genomes
AF:
0.000125
AC:
19
AN:
152138
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000621
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000191
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000171
AC:
43
AN:
251388
Hom.:
0
AF XY:
0.000250
AC XY:
34
AN XY:
135858
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000523
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000211
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.000192
AC:
281
AN:
1461888
Hom.:
0
Cov.:
31
AF XY:
0.000213
AC XY:
155
AN XY:
727244
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.000191
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000510
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000192
Gnomad4 OTH exome
AF:
0.000199
GnomAD4 genome
AF:
0.000125
AC:
19
AN:
152138
Hom.:
0
Cov.:
32
AF XY:
0.0000807
AC XY:
6
AN XY:
74324
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000621
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000191
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000987
Hom.:
0
Bravo
AF:
0.000117
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.000231
AC:
28
EpiCase
AF:
0.000218
EpiControl
AF:
0.000415

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 GeneticsFeb 02, 2022The c.709G>A (p.V237M) alteration is located in exon 9 (coding exon 9) of the SEC14L2 gene. This alteration results from a G to A substitution at nucleotide position 709, causing the valine (V) at amino acid position 237 to be replaced by a methionine (M). 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
0.24
BayesDel_addAF
Benign
-0.41
T
BayesDel_noAF
Benign
-0.48
CADD
Benign
13
DANN
Uncertain
0.98
DEOGEN2
Benign
0.23
T;T;.;.;.;.
Eigen
Benign
-0.70
Eigen_PC
Benign
-0.80
FATHMM_MKL
Benign
0.46
N
LIST_S2
Uncertain
0.96
D;D;D;D;D;D
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.11
T;T;T;T;T;T
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
1.7
L;.;.;L;.;.
MutationTaster
Benign
1.0
N;N;N;N
PrimateAI
Benign
0.35
T
PROVEAN
Benign
0.21
.;N;.;N;N;N
REVEL
Benign
0.13
Sift
Uncertain
0.0020
.;D;.;D;D;D
Sift4G
Uncertain
0.0050
D;D;D;D;D;D
Polyphen
0.13
B;.;B;B;.;.
Vest4
0.32
MVP
0.27
ClinPred
0.094
T
GERP RS
-9.8
Varity_R
0.50
gMVP
0.46

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: rs373330932; hg19: chr22-30811792; API