22-30407590-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

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. 16/22 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

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

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]

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 was made for transcript

Our verdict: Benign. The variant received -20 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_multiple_submitters_no_conflicts, 2 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 the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check.

BS2

High Homozygotes in GnomAd4 at 52 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEC14L2	NM_012429.5 link	c.410A>G	p.His137Arg	missense_variant	Exon 5 of 12	ENST00000615189.5	NP_036561.1	O76054-1A0A024R1I5
SEC14L2	NM_033382.3 link	c.410A>G	p.His137Arg	missense_variant	Exon 5 of 11		NP_203740.1	O76054-4
SEC14L2	NM_001291932.2 link	c.248A>G	p.His83Arg	missense_variant	Exon 4 of 11		NP_001278861.1	B7Z3Z8
SEC14L2	NM_001204204.3 link	c.174+1205A>G		intron_variant	Intron 3 of 9		NP_001191133.1	O76054-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEC14L2	ENST00000615189.5 link	c.410A>G	p.His137Arg	missense_variant	Exon 5 of 12	1	NM_012429.5	ENSP00000478755.1		O76054-1

Frequencies

GnomAD3 genomes

AF:

0.0140

AC:

2130

AN:

152130

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.00385

AC:

965

AN:

250936

AF XY:

0.00268

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 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.:

Cov.:

AF XY:

0.00130

AC XY:

945

AN XY:

727048

show subpopulations

Gnomad4 AFR exome

AF:

0.0510

AC:

1708

AN:

33478

Gnomad4 AMR exome

AF:

0.00297

AC:

133

AN:

44718

Gnomad4 ASJ exome

AF:

0.0000765

AC:

AN:

26128

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

39692

Gnomad4 SAS exome

AF:

0.000104

AC:

AN:

86250

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

53288

Gnomad4 NFE exome

AF:

0.000115

AC:

128

AN:

1111854

Gnomad4 Remaining exome

AF:

0.00336

AC:

203

AN:

60380

Heterozygous variant carriers

111

223

334

446

557

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

112

168

224

280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0140

AC:

2134

AN:

152248

Hom.:

Cov.:

AF XY:

0.0137

AC XY:

1019

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0487

AC:

0.0487071

AN:

0.0487071

Gnomad4 AMR

AF:

0.00477

AC:

0.00477436

AN:

0.00477436

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.000207

AC:

0.000207039

AN:

0.000207039

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.000191

AC:

0.000191126

AN:

0.000191126

Gnomad4 OTH

AF:

0.0104

AC:

0.0104265

AN:

0.0104265

Heterozygous variant carriers

102

205

307

410

512

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00555

Hom.:

Bravo

AF:

0.0157

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0508

AC:

224

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.00450

AC:

546

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 13, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.048

BayesDel_addAF

Benign

-0.63

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

LIST_S2

Benign

0.024

T;T;T;T

MetaRNN

Benign

0.0027

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-1.9

N;.;.;N

PrimateAI

Benign

0.21

PROVEAN

Benign

1.5

.;N;.;N

REVEL

Benign

0.048

Sift

Benign

0.65

.;T;.;T

Sift4G

Benign

0.52

T;T;T;T

Polyphen

0.0

B;.;B;B

Vest4

0.063

MVP

0.67

ClinPred

0.0039

GERP RS

-4.2

Varity_R

0.15

gMVP

0.28

Mutation Taster

=87/13

polymorphism

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