NM_006364.4:c.1987-82A>G

Variant names:

• chr14-39040969-T-C
• rs62001129
• NM_006364.4:c.1987-82A>G

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.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
• Publications: 2 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 -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 VariationId 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.

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.1987-82A>G		intron	N/A	NP_006355.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC23A	ENST00000307712.11	TSL:1 MANE Select	c.1987-82A>G		intron	N/A	ENSP00000306881.6	Q15436-1
	SEC23A	ENST00000554615.1	TSL:1	n.465A>G		non_coding_transcript_exon	Exon 1 of 2
	SEC23A	ENST00000857742.1		c.2059-82A>G		intron	N/A	ENSP00000527801.1

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

African (AFR) AF: 0.148 AC: 4278 AN: 28906

American (AMR) AF: 0.228 AC: 6035 AN: 26446

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 3502 AN: 22942

East Asian (EAS) AF: 0.181 AC: 6371 AN: 35248

South Asian (SAS) AF: 0.157 AC: 11095 AN: 70752

European-Finnish (FIN) AF: 0.152 AC: 5678 AN: 37424

Middle Eastern (MID) AF: 0.189 AC: 739 AN: 3902

European-Non Finnish (NFE) AF: 0.141 AC: 147342 AN: 1046030

Other (OTH) AF: 0.150 AC: 8257 AN: 55162

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

African (AFR) AF: 0.140 AC: 5824 AN: 41482

American (AMR) AF: 0.183 AC: 2797 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 526 AN: 3468

East Asian (EAS) AF: 0.174 AC: 899 AN: 5176

South Asian (SAS) AF: 0.147 AC: 707 AN: 4820

European-Finnish (FIN) AF: 0.154 AC: 1637 AN: 10602

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

European-Non Finnish (NFE) AF: 0.142 AC: 9680 AN: 67992

Other (OTH) AF: 0.150 AC: 318 AN: 2114

Alfa AF: 0.134 Hom.: 150

Bravo AF: 0.154

Asia WGS AF: 0.158 AC: 548 AN: 3472

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.8
DANN	Benign	0.63
PhyloP100		0.027
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: rs62001129; hg19: chr14-39510173;