22-30397150-C-G

Position:

chr22-30397150-C-G

Variant summary

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

The NM_012429.5(SEC14L2):c.34C>G(p.Gln12Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000116 in 1,545,080 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

SEC14L2
NM_012429.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.96

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]

SEC14L2 links:

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]

RNF215 links:

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=0.23167425).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SEC14L2	NM_012429.5 linkuse as main transcript	c.34C>G	p.Gln12Glu	missense_variant	1/12	ENST00000615189.5
SEC14L2	NM_033382.3 linkuse as main transcript	c.34C>G	p.Gln12Glu	missense_variant	1/11
SEC14L2	NM_001204204.3 linkuse as main transcript	c.34C>G	p.Gln12Glu	missense_variant	1/10
SEC14L2	NM_001291932.2 linkuse as main transcript	c.-53C>G		5_prime_UTR_variant	1/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEC14L2	ENST00000615189.5 linkuse as main transcript	c.34C>G	p.Gln12Glu	missense_variant	1/12	1	NM_012429.5	P1	O76054-1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000681

AC:

AN:

146736

Hom.:

AF XY:

0.0000513

AC XY:

AN XY:

78026

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000329

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:

0.0000183

Gnomad OTH exome

AF:

0.000240

GnomAD4 exome

AF:

0.0000101

AC:

AN:

1392996

Hom.:

Cov.:

AF XY:

0.00000873

AC XY:

AN XY:

687008

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000312

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:

0.00000279

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152084

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000718

ExAC

AF:

0.0000112

AC:

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

Dec 28, 2023

The c.34C>G (p.Q12E) alteration is located in exon 1 (coding exon 1) of the SEC14L2 gene. This alteration results from a C to G substitution at nucleotide position 34, causing the glutamine (Q) at amino acid position 12 to be replaced by a glutamic acid (E). 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

0.27

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.14

T;.;.

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.89

D;D;D

M_CAP

Benign

0.030

MetaRNN

Benign

0.23

T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Pathogenic

3.2

M;M;M

MutationTaster

Benign

1.0

D;D;D;N

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-1.9

.;N;N

REVEL

Benign

0.14

Sift

Pathogenic

0.0

.;D;D

Sift4G

Uncertain

0.010

D;D;D

Polyphen

0.81

P;P;.

Vest4

0.41

MutPred

0.57

Loss of MoRF binding (P = 0.0295);Loss of MoRF binding (P = 0.0295);Loss of MoRF binding (P = 0.0295);

MVP

0.32

ClinPred

0.62

GERP RS

4.2

Varity_R

0.74

gMVP

0.80

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over