rs17108797

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_006364.4(SEC23A):c.927T>C(p.Pro309Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0589 in 1,613,692 control chromosomes in the GnomAD database, including 3,273 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.047 ( 244 hom., cov: 32)

Exomes 𝑓: 0.060 ( 3029 hom. )

Consequence

SEC23A
NM_006364.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.0660

Publications

11 publications found

Variant links:

Genes affected

SEC23A (HGNC:10701): (SEC23 homolog A, COPII coat complex component) The protein encoded by this gene is a member of the SEC23 subfamily of the SEC23/SEC24 family. It is part of a protein complex and found in the ribosome-free transitional face of the endoplasmic reticulum (ER) and associated vesicles. This protein has similarity to yeast Sec23p component of COPII. COPII is the coat protein complex responsible for vesicle budding from the ER. The encoded protein is suggested to play a role in the ER-Golgi protein trafficking. [provided by RefSeq, Jul 2008]

SEC23A Gene-Disease associations (from GenCC):

craniolenticulosutural dysplasia
Inheritance: AR, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P

SEC23A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 14-39075995-A-G is Benign according to our data. Variant chr14-39075995-A-G is described in ClinVar as Benign. ClinVar VariationId is 464900.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.066 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
SEC23A	NM_006364.4 link	c.927T>C	p.Pro309Pro	synonymous_variant	Exon 8 of 20	ENST00000307712.11	NP_006355.2
SEC23A	XM_005267262.2 link	c.927T>C	p.Pro309Pro	synonymous_variant	Exon 8 of 21		XP_005267319.1
SEC23A	XM_011536355.4 link	c.927T>C	p.Pro309Pro	synonymous_variant	Exon 8 of 21		XP_011534657.1
SEC23A	XM_017020928.3 link	c.927T>C	p.Pro309Pro	synonymous_variant	Exon 8 of 20		XP_016876417.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
SEC23A	ENST00000307712.11 link	c.927T>C	p.Pro309Pro	synonymous_variant	Exon 8 of 20	1	NM_006364.4	ENSP00000306881.6
SEC23A	ENST00000545328.6 link	c.840T>C	p.Pro280Pro	synonymous_variant	Exon 7 of 19	2		ENSP00000445393.2
SEC23A	ENST00000537403.5 link	c.321T>C	p.Pro107Pro	synonymous_variant	Exon 4 of 16	2		ENSP00000444193.1

Frequencies

GnomAD3 genomes

AF:

0.0472

AC:

7174

AN:

152138

Hom.:

245

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0114

Gnomad AMI

AF:

0.167

Gnomad AMR

AF:

0.0511

Gnomad ASJ

AF:

0.130

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0273

Gnomad FIN

AF:

0.0640

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0637

Gnomad OTH

AF:

0.0737

GnomAD2 exomes

AF:

0.0509

AC:

12795

AN:

251296

AF XY:

0.0527

show subpopulations

Gnomad AFR exome

AF:

0.00947

Gnomad AMR exome

AF:

0.0368

Gnomad ASJ exome

AF:

0.131

Gnomad EAS exome

AF:

0.000381

Gnomad FIN exome

AF:

0.0604

Gnomad NFE exome

AF:

0.0658

Gnomad OTH exome

AF:

0.0703

GnomAD4 exome

AF:

0.0601

AC:

87860

AN:

1461436

Hom.:

3029

Cov.:

AF XY:

0.0599

AC XY:

43526

AN XY:

727038

show subpopulations

African (AFR)

AF:

0.00998

AC:

334

AN:

33476

American (AMR)

AF:

0.0388

AC:

1734

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.128

AC:

3333

AN:

26130

East Asian (EAS)

AF:

0.000277

AC:

AN:

39676

South Asian (SAS)

AF:

0.0301

AC:

2596

AN:

86238

European-Finnish (FIN)

AF:

0.0606

AC:

3235

AN:

53418

Middle Eastern (MID)

AF:

0.0689

AC:

397

AN:

5766

European-Non Finnish (NFE)

AF:

0.0652

AC:

72449

AN:

1111632

Other (OTH)

AF:

0.0625

AC:

3771

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

3898

7797

11695

15594

19492

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2644

5288

7932

10576

13220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0471

AC:

7168

AN:

152256

Hom.:

244

Cov.:

AF XY:

0.0469

AC XY:

3491

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.0113

AC:

471

AN:

41556

American (AMR)

AF:

0.0510

AC:

780

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.130

AC:

450

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5188

South Asian (SAS)

AF:

0.0275

AC:

133

AN:

4828

European-Finnish (FIN)

AF:

0.0640

AC:

679

AN:

10602

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0637

AC:

4330

AN:

68010

Other (OTH)

AF:

0.0724

AC:

153

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

343

687

1030

1374

1717

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

164

246

328

410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0641

Hom.:

786

Bravo

AF:

0.0457

Asia WGS

AF:

0.0140

AC:

AN:

3476

EpiCase

AF:

0.0732

EpiControl

AF:

0.0732

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Oct 16, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

SEC23A-related disorder

Benign:1

Jul 15, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Craniolenticulosutural dysplasia

Benign:1

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

9.0

(source)

DANN

Benign

0.70

PhyloP100

0.066

Mutation Taster

=87/13

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over