14-39033426-G-GAA

Position:

• chr14-39033426-G-GAA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_006364.4(SEC23A):​c.2209-99_2209-98insTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0149 in 60,114 control chromosomes in the GnomAD database, including 5 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.019 (2 hom., cov: 0)
  • Exomes 𝑓: 0.014 (3 hom.)
• Consequence: SEC23A NM_006364.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.987

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 -10 ACMG points.

• BP6: Variant 14-39033426-G-GAA is Benign according to our data. Variant chr14-39033426-G-GAA is described in ClinVar as [Benign]. Clinvar id is 1280265.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEC23A	NM_006364.4	c.2209-99_2209-98insTT		intron_variant		ENST00000307712.11	NP_006355.2
SEC23A	XM_005267262.2	c.2281-99_2281-98insTT		intron_variant			XP_005267319.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEC23A	ENST00000307712.11	c.2209-99_2209-98insTT		intron_variant		1	NM_006364.4	ENSP00000306881	P1

Frequencies

GnomAD3 genomes AF: 0.0186 AC: 220 AN: 11818 Hom.: 2 Cov.: 0

Gnomad AFR AF: 0.0518

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00274

Gnomad ASJ AF: 0.0149

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000231

Gnomad OTH AF: 0.0149

GnomAD4 exome AF: 0.0140 AC: 678 AN: 48278 Hom.: 3 AF XY: 0.0129 AC XY: 332 AN XY: 25650

Gnomad4 AFR exome AF: 0.190

Gnomad4 AMR exome AF: 0.0170

Gnomad4 ASJ exome AF: 0.0742

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000345

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00225

Gnomad4 OTH exome AF: 0.0262

GnomAD4 genome AF: 0.0186 AC: 220 AN: 11836 Hom.: 2 Cov.: 0 AF XY: 0.0182 AC XY: 108 AN XY: 5942

Gnomad4 AFR AF: 0.0518

Gnomad4 AMR AF: 0.00274

Gnomad4 ASJ AF: 0.0149

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000231

Gnomad4 OTH AF: 0.0139

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 23, 2021

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1375186118; hg19: chr14-39502630;