rs147410912

Positions:

chr20-18535655-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_006363.6(SEC23B):c.1317G>T(p.Glu439Asp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000307 in 1,613,780 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0016 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00017 ( 3 hom. )

Consequence

SEC23B
NM_006363.6 missense, splice_region

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:2

Conservation

PhyloP100: 0.00500

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012220919).

BP6

Variant 20-18535655-G-T is Benign according to our data. Variant chr20-18535655-G-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 532197.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=2}.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00158 (240/152280) while in subpopulation AFR AF= 0.00546 (227/41564). AF 95% confidence interval is 0.00488. There are 1 homozygotes in gnomad4. There are 110 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 3 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEC23B	NM_006363.6 linkuse as main transcript	c.1317G>T	p.Glu439Asp	missense_variant, splice_region_variant	12/20	ENST00000650089.1	NP_006354.2	Q15437

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEC23B	ENST00000650089.1 linkuse as main transcript	c.1317G>T	p.Glu439Asp	missense_variant, splice_region_variant	12/20		NM_006363.6	ENSP00000497473.1		Q15437

Frequencies

GnomAD3 genomes

AF:

0.00158

AC:

240

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00548

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000453

AC:

114

AN:

251434

Hom.:

AF XY:

0.000302

AC XY:

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.00597

Gnomad AMR exome

AF:

0.000318

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.000815

GnomAD4 exome

AF:

0.000174

AC:

255

AN:

1461500

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

117

AN XY:

727084

show subpopulations

Gnomad4 AFR exome

AF:

0.00616

Gnomad4 AMR exome

AF:

0.000358

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.000447

GnomAD4 genome

AF:

0.00158

AC:

240

AN:

152280

Hom.:

Cov.:

AF XY:

0.00148

AC XY:

110

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00546

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000978

Hom.:

Bravo

AF:

0.00191

ESP6500AA

AF:

0.00567

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000486

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:2

Uncertain significance, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Feb 03, 2022	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	May 03, 2022	- -

SEC23B-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 30, 2024

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

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

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Uncertain

-0.030

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.088

T;T;T;.;T;T

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.80

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.97

.;.;.;D;.;D

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.012

T;T;T;T;T;T

MetaSVM

Benign

-0.55

MutationAssessor

Uncertain

2.5

M;M;M;.;M;M

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-2.3

N;N;N;.;.;N

REVEL

Uncertain

0.51

Sift

Benign

0.076

T;T;T;.;.;T

Sift4G

Benign

0.18

T;T;T;.;.;T

Polyphen

0.0010

B;B;B;.;B;B

Vest4

0.70

MutPred

0.50

Loss of disorder (P = 0.1294);Loss of disorder (P = 0.1294);Loss of disorder (P = 0.1294);.;Loss of disorder (P = 0.1294);Loss of disorder (P = 0.1294);

MVP

0.76

MPC

0.21

ClinPred

0.038

GERP RS

-3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.24

gMVP

0.52

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