Variant 4-109463447-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_006323.5(SEC24B):c.680T>C(p.Phe227Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000515 in 1,614,110 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00052 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00051 ( 3 hom. )

Consequence

SEC24B
NM_006323.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.61

Variant links:

Genes affected

SEC24B (HGNC:10704): (SEC24 homolog B, COPII coat complex component) The protein encoded by this gene is a member of the SEC24 subfamily of the SEC23/SEC24 family, which is involved in vesicle trafficking. The encoded protein is thought to be a cargo-binding component of the COPII vesicle, and is thought to be involved in the transport of secretory proteins from the endoplasmic reticulum to the Golgi apparatus. Mutations in this gene have been associated with neural tube defects, and are thought to be a result of a disruption in interactions with the protein encoded by the VANGL planar cell polarity protein 2 (VANGL2) gene. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

SEC24B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008335501).

BS2

High AC in GnomAd4 at 79 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEC24B	NM_006323.5 linkuse as main transcript	c.680T>C	p.Phe227Ser	missense_variant	2/24	ENST00000265175.5	NP_006314.2	O95487-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SEC24B	ENST00000265175.5 linkuse as main transcript	c.680T>C	p.Phe227Ser	missense_variant	2/24	1	NM_006323.5	ENSP00000265175.4	O95487-1
SEC24B	ENST00000504968.6 linkuse as main transcript	c.773T>C	p.Phe258Ser	missense_variant	3/25	1		ENSP00000428564.1	O95487-3
SEC24B	ENST00000399100.6 linkuse as main transcript	c.680T>C	p.Phe227Ser	missense_variant	2/23	1		ENSP00000382051.2	O95487-2

Frequencies

GnomAD3 genomes

AF:

0.000519

AC:

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00404

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000559

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000816

AC:

204

AN:

249966

Hom.:

AF XY:

0.000893

AC XY:

121

AN XY:

135566

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000492

Gnomad ASJ exome

AF:

0.00546

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00140

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000697

Gnomad OTH exome

AF:

0.00165

GnomAD4 exome

AF:

0.000514

AC:

752

AN:

1461892

Hom.:

Cov.:

AF XY:

0.000575

AC XY:

418

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000514

Gnomad4 ASJ exome

AF:

0.00559

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00138

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000340

Gnomad4 OTH exome

AF:

0.000878

GnomAD4 genome

AF:

0.000519

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.000537

AC XY:

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.000393

Gnomad4 ASJ

AF:

0.00404

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000559

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000922

Hom.:

Bravo

AF:

0.000533

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000469

AC:

ExAC

AF:

0.000726

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00104

EpiControl

AF:

0.00113

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2024

SEC24B: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.20

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.16

.;.;T

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.17

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.81

T;T;T

M_CAP

Benign

0.076

MetaRNN

Benign

0.0083

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.5

.;L;L

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.52

N;N;N

REVEL

Benign

0.24

Sift

Pathogenic

0.0

D;D;D

Sift4G

Benign

0.41

T;T;T

Polyphen

0.49, 0.94

.;P;P

Vest4

0.57

MVP

0.41

MPC

0.54

ClinPred

0.097

GERP RS

4.4

Varity_R

0.17

gMVP

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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