4-118723567-TAAG-T
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PM4_Supporting
The NM_014822.4(SEC24D):βc.3044_3046delβ(p.Ser1015del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,638 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (β ).
Frequency
Genomes: π 0.000046 ( 0 hom., cov: 32)
Exomes π: 0.0000021 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
SEC24D
NM_014822.4 inframe_deletion
NM_014822.4 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.60
Genes affected
SEC24D (HGNC:10706): (SEC24 homolog D, COPII coat complex component) The protein encoded by this gene is a member of the SEC24 subfamily of the SEC23/SEC24 family, which is involved in vesicle trafficking. The encoded protein has similarity to yeast Sec24p component of COPII. COPII is the coat protein complex responsible for vesicle budding from the ER. This gene product is implicated in the shaping of the vesicle, and also in cargo selection and concentration. Mutations in this gene have been associated with Cole-Carpenter syndrome, a disorder affecting bone formation, resulting in craniofacial malformations and bones that break easily. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_014822.4. Strenght limited to Supporting due to length of the change: 1aa.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SEC24D | NM_014822.4 | c.3044_3046del | p.Ser1015del | inframe_deletion | 23/23 | ENST00000280551.11 | |
SEC24D | NM_001318066.2 | c.3047_3049del | p.Ser1016del | inframe_deletion | 23/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SEC24D | ENST00000280551.11 | c.3044_3046del | p.Ser1015del | inframe_deletion | 23/23 | 1 | NM_014822.4 | P1 | |
SEC24D | ENST00000511481.5 | c.1937_1939del | p.Ser646del | inframe_deletion | 16/16 | 1 | |||
SEC24D | ENST00000502830.1 | n.373_375del | non_coding_transcript_exon_variant | 2/2 | 2 | ||||
SEC24D | ENST00000505134.5 | n.3175_3177del | non_coding_transcript_exon_variant | 18/18 | 2 |
Frequencies
GnomAD3 genomes AF: 0.00 AC: 7AN: 152000Hom.: 0 Cov.: 32 FAILED QC
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GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251086Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135710
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GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461638Hom.: 0 AF XY: 0.00000138 AC XY: 1AN XY: 727130
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GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000461 AC: 7AN: 152000Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74228
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | May 19, 2022 | 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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals affected with SEC24D-related conditions. This variant is present in population databases (rs761365495, gnomAD 0.02%). This variant, c.3044_3046del, results in the deletion of 1 amino acid(s) of the SEC24D protein (p.Ser1015del), but otherwise preserves the integrity of the reading frame. - |
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at