14-39040727-C-CTT

Variant names:

• chr14-39040727-C-CTT
• rs532535708
• ENST00000554615.1:n.705_706dupAA

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The ENST00000554615.1(SEC23A):​n.705_706dupAA 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 0.00038 in 1,614,166 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0018 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00024 (1 hom.)
• Consequence: SEC23A ENST00000554615.1 non_coding_transcript_exon
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.193
• 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.

• BP6: Variant 14-39040727-C-CTT is Benign according to our data. Variant chr14-39040727-C-CTT is described in ClinVar as [Likely_benign]. Clinvar id is 788183.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEC23A	NM_006364.4	c.2142+3_2142+4dupAA		splice_region_variant, intron_variant	Intron 18 of 19	ENST00000307712.11	NP_006355.2
SEC23A	XM_005267262.2	c.2214+3_2214+4dupAA		splice_region_variant, intron_variant	Intron 19 of 20		XP_005267319.1
SEC23A	XM_011536355.4	c.2214+3_2214+4dupAA		splice_region_variant, intron_variant	Intron 19 of 20		XP_011534657.1
SEC23A	XM_017020928.3	c.2142+3_2142+4dupAA		splice_region_variant, 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.2142+3_2142+4dupAA		splice_region_variant, intron_variant	Intron 18 of 19	1	NM_006364.4	ENSP00000306881.6

Frequencies

GnomAD3 genomes AF: 0.00177 AC: 270 AN: 152204 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00591

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.000561 AC: 141 AN: 251392 AF XY: 0.000346

Gnomad AFR exome AF: 0.00646

Gnomad AMR exome AF: 0.000838

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.000235 AC: 344 AN: 1461844 Hom.: 1 Cov.: 30 AF XY: 0.000193 AC XY: 140 AN XY: 727218

African (AFR) AF: 0.00657 AC: 220 AN: 33478

American (AMR) AF: 0.000850 AC: 38 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.0000459 AC: 51 AN: 1111994

Other (OTH) AF: 0.000563 AC: 34 AN: 60388

GnomAD4 genome AF: 0.00177 AC: 270 AN: 152322 Hom.: 0 Cov.: 32 AF XY: 0.00170 AC XY: 127 AN XY: 74490

African (AFR) AF: 0.00589 AC: 245 AN: 41568

American (AMR) AF: 0.00118 AC: 18 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68024

Other (OTH) AF: 0.00189 AC: 4 AN: 2116

Alfa AF: 0.000955 Hom.: 0

Bravo AF: 0.00230

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Craniolenticulosutural dysplasia Benign:1

Dec 16, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.19

Splicing

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

Other links and lift over

dbSNP: rs532535708; hg19: chr14-39509931;