14-39033422-A-AAATAGAAC

Variant names:

• chr14-39033422-A-AAATAGAAC
• rs11283010
• NM_006364.4:c.2209-95_2209-94insGTTCTATT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_006364.4(SEC23A):​c.2209-95_2209-94insGTTCTATT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.918 in 755,254 control chromosomes in the GnomAD database, including 319,834 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.80 (9193 hom., cov: 0)
  • Exomes 𝑓: 0.92 (310641 hom.)
• Consequence: SEC23A NM_006364.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.00
• Publications: 1 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 -10 ACMG points.

• BP6: Variant 14-39033422-A-AAATAGAAC is Benign according to our data. Variant chr14-39033422-A-AAATAGAAC is described in ClinVar as Benign. ClinVar VariationId is 1283041.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.84 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.2209-95_2209-94insGTTCTATT		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.2209-95_2209-94insGTTCTATT		intron	N/A	ENSP00000306881.6	Q15436-1
	SEC23A	ENST00000554615.1	TSL:1	n.2404-95_2404-94insGTTCTATT		intron	N/A
	SEC23A	ENST00000857742.1		c.2281-95_2281-94insGTTCTATT		intron	N/A	ENSP00000527801.1

Frequencies

GnomAD3 genomes AF: 0.804 AC: 22892 AN: 28458 Hom.: 9181 Cov.: 0

Gnomad AFR AF: 0.836

Gnomad AMI AF: 0.897

Gnomad AMR AF: 0.699

Gnomad ASJ AF: 0.723

Gnomad EAS AF: 0.901

Gnomad SAS AF: 0.674

Gnomad FIN AF: 0.814

Gnomad MID AF: 0.625

Gnomad NFE AF: 0.816

Gnomad OTH AF: 0.810

GnomAD4 exome AF: 0.922 AC: 670289 AN: 726744 Hom.: 310641 AF XY: 0.919 AC XY: 355151 AN XY: 386488

African (AFR) AF: 0.908 AC: 17270 AN: 19030

American (AMR) AF: 0.847 AC: 32912 AN: 38858

Ashkenazi Jewish (ASJ) AF: 0.913 AC: 18954 AN: 20762

East Asian (EAS) AF: 0.976 AC: 35199 AN: 36070

South Asian (SAS) AF: 0.837 AC: 57264 AN: 68424

European-Finnish (FIN) AF: 0.921 AC: 47610 AN: 51668

Middle Eastern (MID) AF: 0.914 AC: 2516 AN: 2754

European-Non Finnish (NFE) AF: 0.939 AC: 425449 AN: 453236

Other (OTH) AF: 0.921 AC: 33115 AN: 35942

GnomAD4 genome AF: 0.804 AC: 22926 AN: 28510 Hom.: 9193 Cov.: 0 AF XY: 0.798 AC XY: 11802 AN XY: 14794

African (AFR) AF: 0.836 AC: 8876 AN: 10618

American (AMR) AF: 0.698 AC: 2129 AN: 3052

Ashkenazi Jewish (ASJ) AF: 0.723 AC: 337 AN: 466

East Asian (EAS) AF: 0.899 AC: 620 AN: 690

South Asian (SAS) AF: 0.673 AC: 898 AN: 1334

European-Finnish (FIN) AF: 0.814 AC: 1469 AN: 1804

Middle Eastern (MID) AF: 0.620 AC: 31 AN: 50

European-Non Finnish (NFE) AF: 0.816 AC: 8171 AN: 10012

Other (OTH) AF: 0.800 AC: 325 AN: 406

Alfa AF: 0.924 Hom.: 5063

Bravo AF: 0.924

Asia WGS AF: 0.664 AC: 1015 AN: 1524

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs11283010; hg19: chr14-39502626;