Variant chr4-109433981-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_006323.5(SEC24B):c.112C>T(p.Pro38Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000099 in 1,202,284 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. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P38A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000095 ( 0 hom. )

Consequence

SEC24B
NM_006323.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.342

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.10701257).

BS2

High AC in GnomAd4 at 19 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEC24B	NM_006323.5 linkuse as main transcript	c.112C>T	p.Pro38Ser	missense_variant	1/24	ENST00000265175.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEC24B	ENST00000265175.5 linkuse as main transcript	c.112C>T	p.Pro38Ser	missense_variant	1/24	1	NM_006323.5	A2	O95487-1
SEC24B	ENST00000504968.6 linkuse as main transcript	c.112C>T	p.Pro38Ser	missense_variant	1/25	1		A2	O95487-3
SEC24B	ENST00000399100.6 linkuse as main transcript	c.112C>T	p.Pro38Ser	missense_variant	1/23	1		P2	O95487-2

Frequencies

GnomAD3 genomes

AF:

0.000126

AC:

AN:

150212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000729

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000663

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:

0.000222

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000951

AC:

100

AN:

1052072

Hom.:

Cov.:

AF XY:

0.0000920

AC XY:

AN XY:

499950

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:

0.0000452

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000105

Gnomad4 OTH exome

AF:

0.0000736

GnomAD4 genome

AF:

0.000126

AC:

AN:

150212

Hom.:

Cov.:

AF XY:

0.0000819

AC XY:

AN XY:

73282

show subpopulations

Gnomad4 AFR

AF:

0.0000729

Gnomad4 AMR

AF:

0.0000663

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000222

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000110

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 12, 2022

The c.112C>T (p.P38S) 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 112, causing the proline (P) at amino acid position 38 to be replaced by a serine (S). 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

0.077

BayesDel_addAF

Benign

-0.049

BayesDel_noAF

Benign

-0.31

CADD

Benign

9.0

DANN

Benign

0.95

DEOGEN2

Benign

0.12

.;.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.056

LIST_S2

Benign

0.41

T;T;T

M_CAP

Pathogenic

0.70

MetaRNN

Benign

0.11

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.0

N;N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.68

PROVEAN

Benign

0.11

N;N;N

REVEL

Benign

0.14

Sift

Benign

0.072

T;T;T

Sift4G

Benign

0.28

T;T;T

Polyphen

0.025, 0.014

.;B;B

Vest4

0.071

MutPred

0.23

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

0.49

MPC

0.14

ClinPred

0.074

GERP RS

1.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.6

Varity_R

0.029

gMVP

0.12

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