20-18532728-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006363.6(SEC23B):c.1298C>T(p.Pro433Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.133 in 1,611,526 control chromosomes in the GnomAD database, including 15,733 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P433P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.10 ( 1072 hom., cov: 32)

Exomes 𝑓: 0.14 ( 14661 hom. )

Consequence

SEC23B
NM_006363.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 7.34

Publications

36 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002571702).

BP6

Variant 20-18532728-C-T is Benign according to our data. Variant chr20-18532728-C-T is described in ClinVar as Benign. ClinVar VariationId is 95380.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEC23B	NM_006363.6 link	c.1298C>T	p.Pro433Leu	missense_variant	Exon 11 of 20	ENST00000650089.1	NP_006354.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEC23B	ENST00000650089.1 link	c.1298C>T	p.Pro433Leu	missense_variant	Exon 11 of 20		NM_006363.6	ENSP00000497473.1

Frequencies

GnomAD3 genomes

AF:

0.102

AC:

15548

AN:

152066

Hom.:

1074

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0249

Gnomad AMI

AF:

0.143

Gnomad AMR

AF:

0.0936

Gnomad ASJ

AF:

0.0539

Gnomad EAS

AF:

0.00308

Gnomad SAS

AF:

0.0911

Gnomad FIN

AF:

0.193

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.148

Gnomad OTH

AF:

0.0890

GnomAD2 exomes

AF:

0.114

AC:

28684

AN:

251392

AF XY:

0.118

show subpopulations

Gnomad AFR exome

AF:

0.0212

Gnomad AMR exome

AF:

0.0963

Gnomad ASJ exome

AF:

0.0653

Gnomad EAS exome

AF:

0.00196

Gnomad FIN exome

AF:

0.188

Gnomad NFE exome

AF:

0.146

Gnomad OTH exome

AF:

0.116

GnomAD4 exome

AF:

0.136

AC:

198794

AN:

1459342

Hom.:

14661

Cov.:

AF XY:

0.135

AC XY:

98314

AN XY:

726116

show subpopulations

African (AFR)

AF:

0.0203

AC:

680

AN:

33454

American (AMR)

AF:

0.0970

AC:

4337

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0595

AC:

1554

AN:

26122

East Asian (EAS)

AF:

0.00202

AC:

AN:

39696

South Asian (SAS)

AF:

0.0977

AC:

8424

AN:

86228

European-Finnish (FIN)

AF:

0.182

AC:

9719

AN:

53402

Middle Eastern (MID)

AF:

0.0744

AC:

429

AN:

5764

European-Non Finnish (NFE)

AF:

0.150

AC:

166110

AN:

1109628

Other (OTH)

AF:

0.124

AC:

7461

AN:

60326

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

7898

15796

23694

31592

39490

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5758

11516

17274

23032

28790

<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:

0.102

AC:

15544

AN:

152184

Hom.:

1072

Cov.:

AF XY:

0.104

AC XY:

7762

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.0248

AC:

1032

AN:

41552

American (AMR)

AF:

0.0936

AC:

1429

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.0539

AC:

187

AN:

3470

East Asian (EAS)

AF:

0.00289

AC:

AN:

5188

South Asian (SAS)

AF:

0.0916

AC:

441

AN:

4816

European-Finnish (FIN)

AF:

0.193

AC:

2044

AN:

10574

Middle Eastern (MID)

AF:

0.0748

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.148

AC:

10060

AN:

67998

Other (OTH)

AF:

0.0871

AC:

184

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

688

1377

2065

2754

3442

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

182

364

546

728

910

<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:

0.125

Hom.:

2769

Bravo

AF:

0.0907

TwinsUK

AF:

0.145

AC:

536

ALSPAC

AF:

0.156

AC:

603

ESP6500AA

AF:

0.0302

AC:

133

ESP6500EA

AF:

0.144

AC:

1235

ExAC

AF:

0.112

AC:

13624

Asia WGS

AF:

0.0410

AC:

141

AN:

3478

EpiCase

AF:

0.140

EpiControl

AF:

0.135

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Sep 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 29, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 15, 2013

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

Feb 03, 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 12, 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

Benign

0.088

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.23

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.074

T;T;T;.;T;T

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.86

.;.;.;D;.;D

MetaRNN

Benign

0.0026

T;T;T;T;T;T

MetaSVM

Benign

-0.77

MutationAssessor

Pathogenic

3.5

M;M;M;.;M;M

PhyloP100

7.3

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-3.6

D;D;D;.;.;D

REVEL

Uncertain

0.47

Sift

Uncertain

0.013

D;D;D;.;.;D

Sift4G

Uncertain

0.013

D;D;D;.;.;D

Polyphen

0.50

P;P;P;.;P;P

Vest4

0.17

MPC

0.20

ClinPred

0.093

GERP RS

4.8

Varity_R

0.36

gMVP

0.43

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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