rs17108797

Positions:

• chr14-39075995-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_006364.4(SEC23A):​c.927T>C​(p.Pro309=) 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:3
• Conservation: PhyloP100: 0.0660

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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/exons	MANE	UniProt
SEC23A	NM_006364.4	c.927T>C	p.Pro309=	synonymous_variant	8/20	ENST00000307712.11
SEC23A	XM_005267262.2	c.927T>C	p.Pro309=	synonymous_variant	8/21
SEC23A	XM_011536355.4	c.927T>C	p.Pro309=	synonymous_variant	8/21
SEC23A	XM_017020928.3	c.927T>C	p.Pro309=	synonymous_variant	8/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEC23A	ENST00000307712.11	c.927T>C	p.Pro309=	synonymous_variant	8/20	1	NM_006364.4	P1
SEC23A	ENST00000545328.6	c.840T>C	p.Pro280=	synonymous_variant	7/19	2
SEC23A	ENST00000537403.5	c.321T>C	p.Pro107=	synonymous_variant	4/16	2

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

GnomAD3 exomes AF: 0.0509 AC: 12795 AN: 251296 Hom.: 443 AF XY: 0.0527 AC XY: 7154 AN XY: 135830

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 SAS exome AF: 0.0272

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

Gnomad4 AFR exome AF: 0.00998

Gnomad4 AMR exome AF: 0.0388

Gnomad4 ASJ exome AF: 0.128

Gnomad4 EAS exome AF: 0.000277

Gnomad4 SAS exome AF: 0.0301

Gnomad4 FIN exome AF: 0.0606

Gnomad4 NFE exome AF: 0.0652

Gnomad4 OTH exome AF: 0.0625

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

Gnomad4 AFR AF: 0.0113

Gnomad4 AMR AF: 0.0510

Gnomad4 ASJ AF: 0.130

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0275

Gnomad4 FIN AF: 0.0640

Gnomad4 NFE AF: 0.0637

Gnomad4 OTH AF: 0.0724

Alfa AF: 0.0665 Hom.: 625

Bravo AF: 0.0457

Asia WGS AF: 0.0140 AC: 49 AN: 3476

EpiCase AF: 0.0732

EpiControl AF: 0.0732

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

SEC23A-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 15, 2019

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). -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 16, 2018

- -

Craniolenticulosutural dysplasia Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 25, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	9.0
DANN	Benign	0.70

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

LitVar

Other links and lift over

dbSNP: rs17108797; hg19: chr14-39545199;