NM_006364.4:c.2208+168C>A

Variant names:

• chr14-39038863-G-T
• rs1555257
• NM_006364.4:c.2208+168C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_006364.4(SEC23A):​c.2208+168C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 151,986 control chromosomes in the GnomAD database, including 11,057 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.37 (11057 hom., cov: 32)
• Consequence: SEC23A NM_006364.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.703
• Publications: 4 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 14-39038863-G-T is Benign according to our data. Variant chr14-39038863-G-T is described in ClinVar as [Benign]. Clinvar id is 1289736.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEC23A	NM_006364.4	c.2208+168C>A		intron_variant	Intron 19 of 19	ENST00000307712.11	NP_006355.2
SEC23A	XM_005267262.2	c.2280+168C>A		intron_variant	Intron 20 of 20		XP_005267319.1
SEC23A	XM_011536355.4	c.2280+168C>A		intron_variant	Intron 20 of 20		XP_011534657.1
SEC23A	XM_017020928.3	c.2208+168C>A		intron_variant	Intron 19 of 19		XP_016876417.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEC23A	ENST00000307712.11	c.2208+168C>A		intron_variant	Intron 19 of 19	1	NM_006364.4	ENSP00000306881.6

Frequencies

GnomAD3 genomes AF: 0.373 AC: 56642 AN: 151868 Hom.: 11052 Cov.: 32

Gnomad AFR AF: 0.488

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.255

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.380

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.373 AC: 56680 AN: 151986 Hom.: 11057 Cov.: 32 AF XY: 0.369 AC XY: 27393 AN XY: 74300

African (AFR) AF: 0.488 AC: 20228 AN: 41434

American (AMR) AF: 0.303 AC: 4628 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 1670 AN: 3466

East Asian (EAS) AF: 0.253 AC: 1311 AN: 5172

South Asian (SAS) AF: 0.340 AC: 1637 AN: 4812

European-Finnish (FIN) AF: 0.314 AC: 3316 AN: 10544

Middle Eastern (MID) AF: 0.442 AC: 129 AN: 292

European-Non Finnish (NFE) AF: 0.333 AC: 22611 AN: 67974

Other (OTH) AF: 0.375 AC: 789 AN: 2104

Alfa AF: 0.356 Hom.: 14162

Bravo AF: 0.378

Asia WGS AF: 0.281 AC: 980 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Sep 05, 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	-0.46
CADD	Benign	11
DANN	Benign	0.79
PhyloP100		0.70
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: rs1555257; hg19: chr14-39508067; COSMIC: COSV56978573;