20-18524556-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 1P and 20B. PP3BP4_StrongBP6_Very_StrongBS1BS2

The NM_006363.6(SEC23B):c.490G>T(p.Val164Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00993 in 1,614,174 control chromosomes in the GnomAD database, including 162 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0077 ( 13 hom., cov: 32)

Exomes 𝑓: 0.010 ( 149 hom. )

Consequence

SEC23B
NM_006363.6 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts U:1B:6

Conservation

PhyloP100: 8.12

Publications

21 publications found

Variant links:

Genes affected

SEC23B (HGNC:10702): (SEC23 homolog B, COPII coat complex component) The protein encoded by this gene is a member of the SEC23 subfamily of the SEC23/SEC24 family, which is involved in vesicle trafficking. The encoded protein has similarity to yeast Sec23p component of COPII. COPII is the coat protein complex responsible for vesicle budding from the ER. The function of this gene product has been implicated in cargo selection and concentration. Multiple alternatively spliced transcript variants have been identified in this gene. [provided by RefSeq, Feb 2010]

SEC23B Gene-Disease associations (from GenCC):

congenital dyserythropoietic anemia type 2
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Laboratory for Molecular Medicine, G2P
Cowden disease
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Cowden syndrome 7
Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
congenital dyserythropoietic anemia
Inheritance: AR Classification: LIMITED Submitted by: Genomics England PanelApp

SEC23B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

PP3

Multiple lines of computational evidence support a deleterious effect 8: AlphaMissense, BayesDel_noAF, Cadd, Eigen, MutationAssessor, phyloP100way_vertebrate, REVEL, REVEL [when BayesDel_addAF, max_spliceai, FATHMM_MKL, MetaRNN, MutationTaster was below the threshold]

BP4

Computational evidence support a benign effect (MetaRNN=0.01537177).

BP6

Variant 20-18524556-G-T is Benign according to our data. Variant chr20-18524556-G-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 95388.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00769 (1171/152296) while in subpopulation SAS AF = 0.0358 (173/4828). AF 95% confidence interval is 0.0315. There are 13 homozygotes in GnomAd4. There are 590 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 13 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEC23B	NM_006363.6 link	c.490G>T	p.Val164Leu	missense_variant	Exon 5 of 20	ENST00000650089.1	NP_006354.2	Q15437

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEC23B	ENST00000650089.1 link	c.490G>T	p.Val164Leu	missense_variant	Exon 5 of 20		NM_006363.6	ENSP00000497473.1		Q15437

Frequencies

GnomAD3 genomes

AF:

0.00770

AC:

1172

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00159

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.00602

Gnomad ASJ

AF:

0.0127

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0358

Gnomad FIN

AF:

0.00537

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0105

Gnomad OTH

AF:

0.00669

GnomAD2 exomes

AF:

0.0108

AC:

2716

AN:

251424

AF XY:

0.0124

show subpopulations

Gnomad AFR exome

AF:

0.00148

Gnomad AMR exome

AF:

0.00468

Gnomad ASJ exome

AF:

0.0191

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00665

Gnomad NFE exome

AF:

0.0103

Gnomad OTH exome

AF:

0.0121

GnomAD4 exome

AF:

0.0102

AC:

14864

AN:

1461878

Hom.:

149

Cov.:

AF XY:

0.0110

AC XY:

8023

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.00122

AC:

AN:

33480

American (AMR)

AF:

0.00494

AC:

221

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0197

AC:

515

AN:

26136

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39700

South Asian (SAS)

AF:

0.0311

AC:

2685

AN:

86256

European-Finnish (FIN)

AF:

0.00696

AC:

372

AN:

53418

Middle Eastern (MID)

AF:

0.0111

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00935

AC:

10392

AN:

1112000

Other (OTH)

AF:

0.00945

AC:

571

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

931

1862

2793

3724

4655

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

406

812

1218

1624

2030

<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:

0.00769

AC:

1171

AN:

152296

Hom.:

Cov.:

AF XY:

0.00792

AC XY:

590

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.00159

AC:

AN:

41556

American (AMR)

AF:

0.00601

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0127

AC:

AN:

3470

East Asian (EAS)

AF:

0.000386

AC:

AN:

5184

South Asian (SAS)

AF:

0.0358

AC:

173

AN:

4828

European-Finnish (FIN)

AF:

0.00537

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0105

AC:

716

AN:

68028

Other (OTH)

AF:

0.00662

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

122

184

245

306

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00891

Hom.:

Bravo

AF:

0.00726

TwinsUK

AF:

0.00755

AC:

ALSPAC

AF:

0.00986

AC:

ESP6500AA

AF:

0.00272

AC:

ESP6500EA

AF:

0.00988

AC:

ExAC

AF:

0.0118

AC:

1432

Asia WGS

AF:

0.0110

AC:

AN:

3478

EpiCase

AF:

0.0115

EpiControl

AF:

0.0107

ClinVar

Significance: Benign/Likely benign

Submissions summary: Uncertain:1Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

May 31, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

SEC23B: BS1, BS2 -

Cowden syndrome 7

Uncertain:1

Jul 11, 2018

OMIM

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:literature only

- -

not specified

Benign:1

Jun 30, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Congenital dyserythropoietic anemia, type II;C4225179:Cowden syndrome 7

Benign:1

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Congenital dyserythropoietic anemia, type II

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.59

BayesDel_addAF

Benign

-0.042

BayesDel_noAF

Pathogenic

0.19

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

T;T;T;T;.;T;T

Eigen

Pathogenic

0.85

Eigen_PC

Pathogenic

0.79

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Pathogenic

0.99

.;.;D;.;D;.;D

MetaRNN

Benign

0.015

T;T;T;T;T;T;T

MetaSVM

Uncertain

0.57

MutationAssessor

Pathogenic

3.6

H;H;.;H;.;H;H

PhyloP100

8.1

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-2.7

D;D;D;D;.;.;D

REVEL

Pathogenic

0.79

Sift

Uncertain

0.010

D;D;D;D;.;.;D

Sift4G

Uncertain

0.012

D;D;D;D;.;.;D

Polyphen

0.87

P;P;.;P;.;P;P

Vest4

0.71

MutPred

0.69

Loss of sheet (P = 0.0104);Loss of sheet (P = 0.0104);Loss of sheet (P = 0.0104);Loss of sheet (P = 0.0104);.;Loss of sheet (P = 0.0104);Loss of sheet (P = 0.0104);

MPC

0.62

ClinPred

0.055

GERP RS

4.9

Varity_R

0.69

gMVP

0.63

Mutation Taster

=97/3

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over