Menu
GeneBe

22-30407590-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_012429.5(SEC14L2):c.410A>G(p.His137Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00269 in 1,613,802 control chromosomes in the GnomAD database, including 94 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.014 ( 52 hom., cov: 32)
Exomes 𝑓: 0.0015 ( 42 hom. )

Consequence

SEC14L2
NM_012429.5 missense

Scores

15

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.532
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 Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0027455986).
BP6
Variant 22-30407590-A-G is Benign according to our data. Variant chr22-30407590-A-G is described in ClinVar as [Benign]. Clinvar id is 791373.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.014 (2134/152248) while in subpopulation AFR AF= 0.0487 (2023/41534). AF 95% confidence interval is 0.0469. There are 52 homozygotes in gnomad4. There are 1019 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd at 52 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SEC14L2NM_012429.5 linkuse as main transcriptc.410A>G p.His137Arg missense_variant 5/12 ENST00000615189.5
SEC14L2NM_033382.3 linkuse as main transcriptc.410A>G p.His137Arg missense_variant 5/11
SEC14L2NM_001291932.2 linkuse as main transcriptc.248A>G p.His83Arg missense_variant 4/11
SEC14L2NM_001204204.3 linkuse as main transcriptc.174+1205A>G intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SEC14L2ENST00000615189.5 linkuse as main transcriptc.410A>G p.His137Arg missense_variant 5/121 NM_012429.5 P1O76054-1

Frequencies

GnomAD3 genomes
AF:
0.0140
AC:
2130
AN:
152130
Hom.:
52
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0487
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00485
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.000191
Gnomad OTH
AF:
0.0105
GnomAD3 exomes
AF:
0.00385
AC:
965
AN:
250936
Hom.:
24
AF XY:
0.00268
AC XY:
364
AN XY:
135656
show subpopulations
Gnomad AFR exome
AF:
0.0504
Gnomad AMR exome
AF:
0.00286
Gnomad ASJ exome
AF:
0.0000994
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000131
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000256
Gnomad OTH exome
AF:
0.00212
GnomAD4 exome
AF:
0.00151
AC:
2200
AN:
1461554
Hom.:
42
Cov.:
31
AF XY:
0.00130
AC XY:
945
AN XY:
727048
show subpopulations
Gnomad4 AFR exome
AF:
0.0510
Gnomad4 AMR exome
AF:
0.00297
Gnomad4 ASJ exome
AF:
0.0000765
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000104
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000115
Gnomad4 OTH exome
AF:
0.00336
GnomAD4 genome
AF:
0.0140
AC:
2134
AN:
152248
Hom.:
52
Cov.:
32
AF XY:
0.0137
AC XY:
1019
AN XY:
74438
show subpopulations
Gnomad4 AFR
AF:
0.0487
Gnomad4 AMR
AF:
0.00477
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000191
Gnomad4 OTH
AF:
0.0104
Alfa
AF:
0.00245
Hom.:
13
Bravo
AF:
0.0157
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.0508
AC:
224
ESP6500EA
AF:
0.000465
AC:
4
ExAC
AF:
0.00450
AC:
546
Asia WGS
AF:
0.00173
AC:
6
AN:
3478
EpiCase
AF:
0.000273
EpiControl
AF:
0.000474

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJun 13, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.048
BayesDel_addAF
Benign
-0.63
T
BayesDel_noAF
Benign
-0.65
Cadd
Benign
0.20
Dann
Benign
0.59
DEOGEN2
Benign
0.051
T;T;.;.
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.034
N
LIST_S2
Benign
0.024
T;T;T;T
MetaRNN
Benign
0.0027
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
-1.9
N;.;.;N
MutationTaster
Benign
1.0
N;N;N;N
PrimateAI
Benign
0.21
T
Sift4G
Benign
0.52
T;T;T;T
Polyphen
0.0
B;.;B;B
Vest4
0.063
MVP
0.67
ClinPred
0.0039
T
GERP RS
-4.2
Varity_R
0.15
gMVP
0.28

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: rs77995868; hg19: chr22-30803579; API