dbSNP rs1325709170: SEC24B:p.Ala36Glu (chr4-109433976-C-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_006323.5(SEC24B):c.107C>A(p.Ala36Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A36V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SEC24B
NM_006323.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.382

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006323.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SEC24B	NM_006323.5	MANE Select	c.107C>A	p.Ala36Glu	missense	Exon 1 of 24	NP_006314.2	O95487-1
SEC24B	NM_001300813.3		c.107C>A	p.Ala36Glu	missense	Exon 1 of 25	NP_001287742.1	O95487-3
SEC24B	NM_001318085.2		c.107C>A	p.Ala36Glu	missense	Exon 1 of 24	NP_001305014.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SEC24B	ENST00000265175.5	TSL:1 MANE Select	c.107C>A	p.Ala36Glu	missense	Exon 1 of 24	ENSP00000265175.4	O95487-1
SEC24B	ENST00000504968.6	TSL:1	c.107C>A	p.Ala36Glu	missense	Exon 1 of 25	ENSP00000428564.1	O95487-3
SEC24B	ENST00000399100.6	TSL:1	c.107C>A	p.Ala36Glu	missense	Exon 1 of 23	ENSP00000382051.2	O95487-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1060176

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

505054

African (AFR)

AF:

0.00

AC:

AN:

21384

American (AMR)

AF:

0.00

AC:

AN:

7118

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12450

East Asian (EAS)

AF:

0.00

AC:

AN:

23050

South Asian (SAS)

AF:

0.00

AC:

AN:

23576

European-Finnish (FIN)

AF:

0.00

AC:

AN:

20286

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2736

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

908500

Other (OTH)

AF:

0.00

AC:

AN:

41076

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

0.00025

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Benign

0.63

DEOGEN2

Benign

0.090

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.27

M_CAP

Benign

0.018

MetaRNN

Benign

0.084

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.0

PhyloP100

0.38

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

0.13

REVEL

Benign

0.12

Sift

Uncertain

0.017

Sift4G

Benign

1.0

Vest4

0.11

MutPred

0.22

Loss of glycosylation at P34 (P = 0.0304)

MVP

0.58

MPC

0.17

ClinPred

0.15

PromoterAI

0.12

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Varity_R

0.086

gMVP

0.076

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.69

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.69

Position offset: -4

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over