20-18532728-C-T

Variant summary

Our verdict is Benign. Variant got -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:6

Conservation

PhyloP100: 7.34

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 95380.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-18532728-C-T is described in Lovd as [Benign].

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/exons	MANE	UniProt
SEC23B	NM_006363.6 linkuse as main transcript	c.1298C>T	p.Pro433Leu	missense_variant	11/20	ENST00000650089.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEC23B	ENST00000650089.1 linkuse as main transcript	c.1298C>T	p.Pro433Leu	missense_variant	11/20		NM_006363.6	P1

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

GnomAD3 exomes

AF:

0.114

AC:

28684

AN:

251392

Hom.:

2066

AF XY:

0.118

AC XY:

15976

AN XY:

135856

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 SAS exome

AF:

0.0968

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

Gnomad4 AFR exome

AF:

0.0203

Gnomad4 AMR exome

AF:

0.0970

Gnomad4 ASJ exome

AF:

0.0595

Gnomad4 EAS exome

AF:

0.00202

Gnomad4 SAS exome

AF:

0.0977

Gnomad4 FIN exome

AF:

0.182

Gnomad4 NFE exome

AF:

0.150

Gnomad4 OTH exome

AF:

0.124

GnomAD4 genome

AF:

0.102

AC:

15544

AN:

152184

Hom.:

1072

Cov.:

AF XY:

0.104

AC XY:

7762

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.0248

Gnomad4 AMR

AF:

0.0936

Gnomad4 ASJ

AF:

0.0539

Gnomad4 EAS

AF:

0.00289

Gnomad4 SAS

AF:

0.0916

Gnomad4 FIN

AF:

0.193

Gnomad4 NFE

AF:

0.148

Gnomad4 OTH

AF:

0.0871

Alfa

AF:

0.130

Hom.:

2341

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:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Apr 15, 2013	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 10, 2018	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 30, 2023	- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Congenital dyserythropoietic anemia, type II

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

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

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

MetaRNN

Benign

0.0026

T;T;T;T;T;T

MetaSVM

Benign

-0.77

MutationAssessor

Pathogenic

3.5

M;M;M;.;M;M

MutationTaster

Benign

4.0e-11

P;P;P;P

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

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

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