chr14-39039403-C-T

Variant names:

• chr14-39039403-C-T
• rs1884385
• ENST00000554615.1:n.2031G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006364.4(SEC23A):​c.2143-307G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 283,456 control chromosomes in the GnomAD database, including 3,508 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (1944 hom., cov: 32)
  • Exomes 𝑓: 0.15 (1564 hom.)
• Consequence: SEC23A NM_006364.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.56
• Publications: 0 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: SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 14-39039403-C-T is Benign according to our data. Variant chr14-39039403-C-T is described in ClinVar as [Benign]. Clinvar id is 1181688.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEC23A	NM_006364.4	c.2143-307G>A		intron_variant	Intron 18 of 19	ENST00000307712.11	NP_006355.2
SEC23A	XM_005267262.2	c.2215-307G>A		intron_variant	Intron 19 of 20		XP_005267319.1
SEC23A	XM_011536355.4	c.2215-307G>A		intron_variant	Intron 19 of 20		XP_011534657.1
SEC23A	XM_017020928.3	c.2143-307G>A		intron_variant	Intron 18 of 19		XP_016876417.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEC23A	ENST00000307712.11	c.2143-307G>A		intron_variant	Intron 18 of 19	1	NM_006364.4	ENSP00000306881.6

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23824 AN: 151636 Hom.: 1947 Cov.: 32

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.158

GnomAD4 exome AF: 0.147 AC: 19341 AN: 131704 Hom.: 1564 Cov.: 0 AF XY: 0.147 AC XY: 10189 AN XY: 69500

African (AFR) AF: 0.217 AC: 483 AN: 2222

American (AMR) AF: 0.202 AC: 956 AN: 4740

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 673 AN: 4570

East Asian (EAS) AF: 0.174 AC: 1438 AN: 8260

South Asian (SAS) AF: 0.140 AC: 1390 AN: 9928

European-Finnish (FIN) AF: 0.147 AC: 900 AN: 6140

Middle Eastern (MID) AF: 0.179 AC: 103 AN: 576

European-Non Finnish (NFE) AF: 0.139 AC: 12184 AN: 87402

Other (OTH) AF: 0.154 AC: 1214 AN: 7866

GnomAD4 genome AF: 0.157 AC: 23833 AN: 151752 Hom.: 1944 Cov.: 32 AF XY: 0.158 AC XY: 11691 AN XY: 74178

African (AFR) AF: 0.169 AC: 6956 AN: 41194

American (AMR) AF: 0.187 AC: 2847 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 527 AN: 3468

East Asian (EAS) AF: 0.175 AC: 907 AN: 5172

South Asian (SAS) AF: 0.147 AC: 708 AN: 4818

European-Finnish (FIN) AF: 0.155 AC: 1641 AN: 10566

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9662 AN: 67966

Other (OTH) AF: 0.157 AC: 332 AN: 2108

Alfa AF: 0.145 Hom.: 179

Bravo AF: 0.161

Asia WGS AF: 0.160 AC: 555 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 27, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.10
DANN	Benign	0.28
PhyloP100		-2.6
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: rs1884385; hg19: chr14-39508607; COSMIC: COSV56974969;