14-39040969-T-C

Position:

• chr14-39040969-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006364.4(SEC23A):​c.1987-82A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 1,478,948 control chromosomes in the GnomAD database, including 16,094 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (1753 hom., cov: 32)
  • Exomes 𝑓: 0.15 (14341 hom.)
• Consequence: SEC23A NM_006364.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0270

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 14-39040969-T-C is Benign according to our data. Variant chr14-39040969-T-C is described in ClinVar as [Benign]. Clinvar id is 1291639.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEC23A	NM_006364.4	c.1987-82A>G		intron_variant		ENST00000307712.11	NP_006355.2
SEC23A	XM_005267262.2	c.2059-82A>G		intron_variant			XP_005267319.1
SEC23A	XM_011536355.4	c.2059-82A>G		intron_variant			XP_011534657.1
SEC23A	XM_017020928.3	c.1987-82A>G		intron_variant			XP_016876417.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEC23A	ENST00000307712.11	c.1987-82A>G		intron_variant		1	NM_006364.4	ENSP00000306881	P1

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22636 AN: 152018 Hom.: 1755 Cov.: 32

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.151

GnomAD4 exome AF: 0.146 AC: 193297 AN: 1326812 Hom.: 14341 Cov.: 23 AF XY: 0.147 AC XY: 96022 AN XY: 654174

Gnomad4 AFR exome AF: 0.148

Gnomad4 AMR exome AF: 0.228

Gnomad4 ASJ exome AF: 0.153

Gnomad4 EAS exome AF: 0.181

Gnomad4 SAS exome AF: 0.157

Gnomad4 FIN exome AF: 0.152

Gnomad4 NFE exome AF: 0.141

Gnomad4 OTH exome AF: 0.150

GnomAD4 genome AF: 0.149 AC: 22641 AN: 152136 Hom.: 1753 Cov.: 32 AF XY: 0.149 AC XY: 11096 AN XY: 74394

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.183

Gnomad4 ASJ AF: 0.152

Gnomad4 EAS AF: 0.174

Gnomad4 SAS AF: 0.147

Gnomad4 FIN AF: 0.154

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.150

Alfa AF: 0.134 Hom.: 149

Bravo AF: 0.154

Asia WGS AF: 0.158 AC: 548 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 27, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.8
DANN	Benign	0.63

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

Publications

LitVar

Other links and lift over

dbSNP: rs62001129; hg19: chr14-39510173;