Variant rs757660 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_012429.5(SEC14L2):c.32G>A(p.Arg11Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 1,544,374 control chromosomes in the GnomAD database, including 80,072 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.35 ( 9442 hom., cov: 31)

Exomes 𝑓: 0.32 ( 70630 hom. )

Consequence

SEC14L2
NM_012429.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.318

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:

SEC14L2 (HGNC:):

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0013599396).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEC14L2	NM_012429.5 linkuse as main transcript	c.32G>A	p.Arg11Lys	missense_variant	1/12	ENST00000615189.5	NP_036561.1	O76054-1A0A024R1I5
SEC14L2	NM_033382.3 linkuse as main transcript	c.32G>A	p.Arg11Lys	missense_variant	1/11		NP_203740.1	O76054-4
SEC14L2	NM_001204204.3 linkuse as main transcript	c.32G>A	p.Arg11Lys	missense_variant	1/10		NP_001191133.1	O76054-5
SEC14L2	NM_001291932.2 linkuse as main transcript	c.-55G>A		5_prime_UTR_variant	1/11		NP_001278861.1	B7Z3Z8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEC14L2	ENST00000615189.5 linkuse as main transcript	c.32G>A	p.Arg11Lys	missense_variant	1/12	1	NM_012429.5	ENSP00000478755.1		O76054-1

Frequencies

GnomAD3 genomes

AF:

0.348

AC:

52675

AN:

151420

Hom.:

9428

Cov.:

show subpopulations

Gnomad AFR

AF:

0.407

Gnomad AMI

AF:

0.420

Gnomad AMR

AF:

0.347

Gnomad ASJ

AF:

0.239

Gnomad EAS

AF:

0.371

Gnomad SAS

AF:

0.380

Gnomad FIN

AF:

0.402

Gnomad MID

AF:

0.317

Gnomad NFE

AF:

0.305

Gnomad OTH

AF:

0.329

GnomAD3 exomes

AF:

0.337

AC:

49563

AN:

147020

Hom.:

8638

AF XY:

0.337

AC XY:

26379

AN XY:

78256

show subpopulations

Gnomad AFR exome

AF:

0.397

Gnomad AMR exome

AF:

0.352

Gnomad ASJ exome

AF:

0.240

Gnomad EAS exome

AF:

0.373

Gnomad SAS exome

AF:

0.383

Gnomad FIN exome

AF:

0.400

Gnomad NFE exome

AF:

0.296

Gnomad OTH exome

AF:

0.307

GnomAD4 exome

AF:

0.315

AC:

439203

AN:

1392836

Hom.:

70630

Cov.:

AF XY:

0.317

AC XY:

217877

AN XY:

686992

show subpopulations

Gnomad4 AFR exome

AF:

0.412

Gnomad4 AMR exome

AF:

0.357

Gnomad4 ASJ exome

AF:

0.237

Gnomad4 EAS exome

AF:

0.379

Gnomad4 SAS exome

AF:

0.387

Gnomad4 FIN exome

AF:

0.403

Gnomad4 NFE exome

AF:

0.301

Gnomad4 OTH exome

AF:

0.325

GnomAD4 genome

AF:

0.348

AC:

52731

AN:

151538

Hom.:

9442

Cov.:

AF XY:

0.354

AC XY:

26246

AN XY:

74076

show subpopulations

Gnomad4 AFR

AF:

0.407

Gnomad4 AMR

AF:

0.347

Gnomad4 ASJ

AF:

0.239

Gnomad4 EAS

AF:

0.371

Gnomad4 SAS

AF:

0.379

Gnomad4 FIN

AF:

0.402

Gnomad4 NFE

AF:

0.305

Gnomad4 OTH

AF:

0.337

Alfa

AF:

0.309

Hom.:

14814

Bravo

AF:

0.342

TwinsUK

AF:

0.307

AC:

1139

ALSPAC

AF:

0.296

AC:

1139

ESP6500AA

AF:

0.354

AC:

1467

ESP6500EA

AF:

0.249

AC:

2010

ExAC

AF:

0.186

AC:

15365

Asia WGS

AF:

0.413

AC:

1433

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.78

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.013

T;.;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0078

LIST_S2

Benign

0.015

T;T;T

MetaRNN

Benign

0.0014

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-1.6

N;N;N

PrimateAI

Benign

0.42

PROVEAN

Benign

1.2

.;N;N

REVEL

Benign

0.080

Sift

Benign

1.0

.;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

B;B;.

Vest4

0.020

ClinPred

0.0026

GERP RS

0.65

Varity_R

0.13

gMVP

0.35

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over