rs17108797

Variant names:

• chr14-39075995-A-G
• rs17108797
• NM_006364.4:c.927T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.0660
• Publications: 11 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 -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.

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.927T>C	p.Pro309Pro	synonymous	Exon 8 of 20	NP_006355.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC23A	ENST00000307712.11	TSL:1 MANE Select	c.927T>C	p.Pro309Pro	synonymous	Exon 8 of 20	ENSP00000306881.6	Q15436-1
	SEC23A	ENST00000857742.1		c.927T>C	p.Pro309Pro	synonymous	Exon 8 of 21	ENSP00000527801.1
	SEC23A	ENST00000857743.1		c.927T>C	p.Pro309Pro	synonymous	Exon 8 of 20	ENSP00000527802.1

Frequencies

GnomAD3 genomes AF: 0.0472 AC: 7174 AN: 152138 Hom.: 245 Cov.: 32

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

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.: 32 AF XY: 0.0599 AC XY: 43526 AN XY: 727038

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: 11 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

GnomAD4 genome AF: 0.0471 AC: 7168 AN: 152256 Hom.: 244 Cov.: 32 AF XY: 0.0469 AC XY: 3491 AN XY: 74452

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: 1 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: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0637 AC: 4330 AN: 68010

Other (OTH) AF: 0.0724 AC: 153 AN: 2112

Alfa AF: 0.0641 Hom.: 786

Bravo AF: 0.0457

Asia WGS AF: 0.0140 AC: 49 AN: 3476

EpiCase AF: 0.0732

EpiControl AF: 0.0732

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Craniolenticulosutural dysplasia (1)
-	-	1	SEC23A-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	9.0
DANN	Benign	0.70
PhyloP100		0.066
Mutation Taster		=87/13	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17108797; hg19: chr14-39545199;