NM_006364.4:c.2209-8dupT

Variant names:

• chr14-39033335-G-GA
• rs11418467
• NM_006364.4:c.2209-8dupT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_006364.4(SEC23A):​c.2209-8dupT variant causes a splice region, 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, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.13
• Publications: 9 publications found

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: MODERATE, SUPPORTIVE, LIMITED Submitted by: Orphanet, PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006364.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC23A	NM_006364.4	MANE Select	c.2209-8dupT		splice_region intron	N/A	NP_006355.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC23A	ENST00000307712.11	TSL:1 MANE Select	c.2209-8_2209-7insT		splice_region intron	N/A	ENSP00000306881.6	Q15436-1
	SEC23A	ENST00000554615.1	TSL:1	n.2404-8_2404-7insT		splice_region intron	N/A
	SEC23A	ENST00000857742.1		c.2281-8_2281-7insT		splice_region intron	N/A	ENSP00000527801.1

Frequencies

GnomAD3 genomes AF: 0.811 AC: 23203 AN: 28614 Hom.: 9411 Cov.: 0

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

GnomAD2 exomes AF: 0.915 AC: 229645 AN: 251066 AF XY: 0.913

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 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.: 24 AF XY: 0.924 AC XY: 640201 AN XY: 693010

African (AFR) AF: 0.926 AC: 29491 AN: 31852

American (AMR) AF: 0.854 AC: 38042 AN: 44558

Ashkenazi Jewish (ASJ) AF: 0.919 AC: 23611 AN: 25702

East Asian (EAS) AF: 0.976 AC: 38347 AN: 39304

South Asian (SAS) AF: 0.841 AC: 71143 AN: 84626

European-Finnish (FIN) AF: 0.922 AC: 49209 AN: 53376

Middle Eastern (MID) AF: 0.900 AC: 4959 AN: 5512

European-Non Finnish (NFE) AF: 0.934 AC: 971438 AN: 1039942

Other (OTH) AF: 0.921 AC: 53213 AN: 57748

GnomAD4 genome AF: 0.811 AC: 23231 AN: 28662 Hom.: 9419 Cov.: 0 AF XY: 0.804 AC XY: 11958 AN XY: 14868

African (AFR) AF: 0.850 AC: 9144 AN: 10760

American (AMR) AF: 0.700 AC: 2136 AN: 3052

Ashkenazi Jewish (ASJ) AF: 0.727 AC: 336 AN: 462

East Asian (EAS) AF: 0.899 AC: 633 AN: 704

South Asian (SAS) AF: 0.674 AC: 897 AN: 1330

European-Finnish (FIN) AF: 0.816 AC: 1479 AN: 1812

Middle Eastern (MID) AF: 0.615 AC: 32 AN: 52

European-Non Finnish (NFE) AF: 0.817 AC: 8183 AN: 10010

Other (OTH) AF: 0.800 AC: 320 AN: 400

Alfa AF: 0.922 Hom.: 8881

Asia WGS AF: 0.671 AC: 976 AN: 1450

EpiCase AF: 0.938

EpiControl AF: 0.937

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Craniolenticulosutural dysplasia (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11418467; hg19: chr14-39502539;