Genetic Variant NM_006363.6:c.1298C>A (chr20-18532728-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006363.6(SEC23B):c.1298C>A(p.Pro433Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. P433R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

SEC23B
NM_006363.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.34

Publications

36 publications found

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 Gene-Disease associations (from GenCC):

congenital dyserythropoietic anemia type 2
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, G2P, PanelApp Australia, Laboratory for Molecular Medicine
Cowden disease
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Cowden syndrome 7
Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
congenital dyserythropoietic anemia
Inheritance: AR Classification: LIMITED Submitted by: Genomics England PanelApp

SEC23B links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006363.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SEC23B	NM_006363.6	MANE Select	c.1298C>A	p.Pro433Gln	missense	Exon 11 of 20	NP_006354.2
SEC23B	NM_001172745.3		c.1298C>A	p.Pro433Gln	missense	Exon 11 of 20	NP_001166216.1	Q15437
SEC23B	NM_032985.6		c.1298C>A	p.Pro433Gln	missense	Exon 11 of 20	NP_116780.1	Q15437

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SEC23B	ENST00000650089.1	MANE Select	c.1298C>A	p.Pro433Gln	missense	Exon 11 of 20	ENSP00000497473.1	Q15437
SEC23B	ENST00000336714.8	TSL:1	c.1298C>A	p.Pro433Gln	missense	Exon 11 of 20	ENSP00000338844.3	Q15437
SEC23B	ENST00000377465.6	TSL:1	c.1298C>A	p.Pro433Gln	missense	Exon 11 of 20	ENSP00000366685.1	Q15437

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Uncertain

0.018

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.079

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.035

MetaRNN

Uncertain

0.66

MetaSVM

Uncertain

-0.17

MutationAssessor

Uncertain

2.6

PhyloP100

7.3

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-2.1

REVEL

Uncertain

0.30

Sift

Benign

0.067

Sift4G

Benign

0.10

Polyphen

0.050

Vest4

0.43

MutPred

0.42

Loss of ubiquitination at K431 (P = 0.0638)

MVP

0.87

MPC

0.19

ClinPred

0.92

GERP RS

4.8

Varity_R

0.16

gMVP

0.35

Mutation Taster

=75/25

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

Details are displayed if max score is > 0.2

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