Variant 14-39033335-G-GA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_006364.4(SEC23A):c.2209-8_2209-7insT variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.923 in 1,411,282 control chromosomes in the GnomAD database, including 602,938 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.81 ( 9419 hom., cov: 0)

Exomes 𝑓: 0.93 ( 593519 hom. )

Consequence

SEC23A
NM_006364.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.13

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 14-39033335-G-GA is Benign according to our data. Variant chr14-39033335-G-GA is described in ClinVar as [Benign]. Clinvar id is 683759.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.841 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEC23A	NM_006364.4 linkuse as main transcript	c.2209-8_2209-7insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000307712.11	NP_006355.2
SEC23A	XM_005267262.2 linkuse as main transcript	c.2281-8_2281-7insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			XP_005267319.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEC23A	ENST00000307712.11 linkuse as main transcript	c.2209-8_2209-7insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_006364.4	ENSP00000306881	P1	Q15436-1

Frequencies

GnomAD3 genomes

AF:

0.811

AC:

23203

AN:

28614

Hom.:

9411

Cov.:

show subpopulations

Gnomad AFR

AF:

0.850

Gnomad AMI

AF:

0.887

Gnomad AMR

AF:

0.701

Gnomad ASJ

AF:

0.727

Gnomad EAS

AF:

0.901

Gnomad SAS

AF:

0.675

Gnomad FIN

AF:

0.816

Gnomad MID

AF:

0.620

Gnomad NFE

AF:

0.818

Gnomad OTH

AF:

0.809

GnomAD3 exomes

AF:

0.915

AC:

229645

AN:

251066

Hom.:

105285

AF XY:

0.913

AC XY:

123951

AN XY:

135760

show subpopulations

Gnomad AFR exome

AF:

0.931

Gnomad AMR exome

AF:

0.853

Gnomad ASJ exome

AF:

0.921

Gnomad EAS exome

AF:

0.972

Gnomad SAS exome

AF:

0.841

Gnomad FIN exome

AF:

0.923

Gnomad NFE exome

AF:

0.939

Gnomad OTH exome

AF:

0.918

GnomAD4 exome

AF:

0.925

AC:

1279453

AN:

1382620

Hom.:

593519

Cov.:

AF XY:

0.924

AC XY:

640201

AN XY:

693010

show subpopulations

Gnomad4 AFR exome

AF:

0.926

Gnomad4 AMR exome

AF:

0.854

Gnomad4 ASJ exome

AF:

0.919

Gnomad4 EAS exome

AF:

0.976

Gnomad4 SAS exome

AF:

0.841

Gnomad4 FIN exome

AF:

0.922

Gnomad4 NFE exome

AF:

0.934

Gnomad4 OTH exome

AF:

0.921

GnomAD4 genome

AF:

0.811

AC:

23231

AN:

28662

Hom.:

9419

Cov.:

AF XY:

0.804

AC XY:

11958

AN XY:

14868

show subpopulations

Gnomad4 AFR

AF:

0.850

Gnomad4 AMR

AF:

0.700

Gnomad4 ASJ

AF:

0.727

Gnomad4 EAS

AF:

0.899

Gnomad4 SAS

AF:

0.674

Gnomad4 FIN

AF:

0.816

Gnomad4 NFE

AF:

0.817

Gnomad4 OTH

AF:

0.800

Alfa

AF:

0.922

Hom.:

8881

Asia WGS

AF:

0.671

AC:

976

AN:

1450

EpiCase

AF:

0.938

EpiControl

AF:

0.937

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Craniolenticulosutural dysplasia

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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