14-39040770-T-C
Variant summary
Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_006364.4(SEC23A):c.2104A>G(p.Met702Val) variant causes a missense change. The variant allele was found at a frequency of 0.000471 in 1,614,212 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_006364.4 missense
Scores
Clinical Significance
Conservation
Publications
- craniolenticulosutural dysplasiaInheritance: AR, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P
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ACMG classification
Our verdict: Likely_benign. The variant received -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SEC23A | NM_006364.4 | c.2104A>G | p.Met702Val | missense_variant | Exon 18 of 20 | ENST00000307712.11 | NP_006355.2 | |
SEC23A | XM_005267262.2 | c.2176A>G | p.Met726Val | missense_variant | Exon 19 of 21 | XP_005267319.1 | ||
SEC23A | XM_011536355.4 | c.2176A>G | p.Met726Val | missense_variant | Exon 19 of 21 | XP_011534657.1 | ||
SEC23A | XM_017020928.3 | c.2104A>G | p.Met702Val | missense_variant | Exon 18 of 20 | XP_016876417.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000328 AC: 50AN: 152220Hom.: 0 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.000318 AC: 80AN: 251456 AF XY: 0.000324 show subpopulations
GnomAD4 exome AF: 0.000486 AC: 710AN: 1461874Hom.: 0 Cov.: 30 AF XY: 0.000484 AC XY: 352AN XY: 727236 show subpopulations
GnomAD4 genome AF: 0.000328 AC: 50AN: 152338Hom.: 0 Cov.: 32 AF XY: 0.000228 AC XY: 17AN XY: 74504 show subpopulations
ClinVar
Submissions by phenotype
Craniolenticulosutural dysplasia Pathogenic:1Uncertain:1
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Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SEC23A protein function. ClinVar contains an entry for this variant (Variation ID: 39521). This missense change has been observed in individual(s) with Craniolenticulosutural dysplasia (PMID: 21039434). This variant is present in population databases (rs138568622, gnomAD 0.06%), and has an allele count higher than expected for a pathogenic variant. This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 702 of the SEC23A protein (p.Met702Val). Experimental studies have shown that this missense change affects SEC23A function (PMID: 22298774). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at