ENST00000554615.1:n.2031G>T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000554615.1(SEC23A):​n.2031G>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000757 in 132,058 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000076 (0 hom.)
• Consequence: SEC23A ENST00000554615.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEC23A	NM_006364.4	c.2143-307G>T		intron_variant	Intron 18 of 19	ENST00000307712.11	NP_006355.2
SEC23A	XM_005267262.2	c.2215-307G>T		intron_variant	Intron 19 of 20		XP_005267319.1
SEC23A	XM_011536355.4	c.2215-307G>T		intron_variant	Intron 19 of 20		XP_011534657.1
SEC23A	XM_017020928.3	c.2143-307G>T		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>T		intron_variant	Intron 18 of 19	1	NM_006364.4	ENSP00000306881.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000757 AC: 1 AN: 132058 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 69684

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 2236

American (AMR) AF: 0.00 AC: 0 AN: 4754

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4578

East Asian (EAS) AF: 0.00 AC: 0 AN: 8298

South Asian (SAS) AF: 0.00 AC: 0 AN: 9956

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6150

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 578

European-Non Finnish (NFE) AF: 0.0000114 AC: 1 AN: 87620

Other (OTH) AF: 0.00 AC: 0 AN: 7888

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.087
DANN	Benign	0.36
PhyloP100		-2.6

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;