4-109433970-C-T

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_006323.5(SEC24B):c.101C>T(p.Pro34Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000572 in 1,222,812 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000047 ( 0 hom. )

Consequence

SEC24B
NM_006323.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0960

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:

SEC24B-AS1 (HGNC:44003): (SEC24B antisense RNA 1) This lncRNA contains a single Alu element which, along with 1/2-sbsRNA3, appears to target the 3' UTR Alu element in MTAP. Downregulation of the RNA appears to up-regulate the target. [provided by RefSeq, Feb 2011]

SEC24B-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07927659).

BS2

High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEC24B	NM_006323.5 link	c.101C>T	p.Pro34Leu	missense_variant	Exon 1 of 24	ENST00000265175.5	NP_006314.2	O95487-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEC24B	ENST00000265175.5 link	c.101C>T	p.Pro34Leu	missense_variant	Exon 1 of 24	1	NM_006323.5	ENSP00000265175.4		O95487-1

Frequencies

GnomAD3 genomes

AF:

0.0000133

AC:

AN:

150558

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000662

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000466

AC:

AN:

1072254

Hom.:

Cov.:

AF XY:

0.00000391

AC XY:

AN XY:

511994

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000397

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000437

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000133

AC:

AN:

150558

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73464

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000662

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 16, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.101C>T (p.P34L) alteration is located in exon 1 (coding exon 1) of the SEC24B gene. This alteration results from a C to T substitution at nucleotide position 101, causing the proline (P) at amino acid position 34 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Uncertain

0.045

BayesDel_noAF

Benign

-0.17

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.098

.;.;T

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.53

T;T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.079

T;T;T

MetaSVM

Benign

-0.78

MutationAssessor

Benign

0.0

N;N;N

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.56

N;N;N

REVEL

Benign

0.18

Sift

Pathogenic

0.0

D;D;D

Sift4G

Uncertain

0.033

D;T;T

Vest4

0.13

MutPred

0.26

Loss of glycosylation at P34 (P = 0.0304);Loss of glycosylation at P34 (P = 0.0304);Loss of glycosylation at P34 (P = 0.0304);

MVP

0.36

MPC

0.15

ClinPred

0.25

GERP RS

2.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Varity_R

0.071

gMVP

0.16

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