rs373713956
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_021942.6(TRAPPC11):c.2851+5G>A variant causes a splice donor 5th base, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000564 in 1,612,276 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: 𝑓 0.00033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000028 ( 0 hom. )
Consequence
TRAPPC11
NM_021942.6 splice_donor_5th_base, intron
NM_021942.6 splice_donor_5th_base, intron
Scores
2
Splicing: ADA: 0.9897
1
1
Clinical Significance
Conservation
PhyloP100: 3.17
Genes affected
TRAPPC11 (HGNC:25751): (trafficking protein particle complex subunit 11) The protein encoded by this gene is a subunit of the TRAPP (transport protein particle) tethering complex, which functions in intracellular vesicle trafficking. This subunit is involved in early stage endoplasmic reticulum-to-Golgi vesicle transport. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jan 2013]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRAPPC11 | NM_021942.6 | c.2851+5G>A | splice_donor_5th_base_variant, intron_variant | ENST00000334690.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRAPPC11 | ENST00000334690.11 | c.2851+5G>A | splice_donor_5th_base_variant, intron_variant | 1 | NM_021942.6 | P1 | |||
TRAPPC11 | ENST00000357207.8 | c.2851+5G>A | splice_donor_5th_base_variant, intron_variant | 1 | |||||
TRAPPC11 | ENST00000512476.1 | c.1669+5G>A | splice_donor_5th_base_variant, intron_variant | 1 | |||||
TRAPPC11 | ENST00000505676.5 | c.*965+5G>A | splice_donor_5th_base_variant, intron_variant, NMD_transcript_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.000323 AC: 49AN: 151930Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000800 AC: 20AN: 249918Hom.: 0 AF XY: 0.0000592 AC XY: 8AN XY: 135084
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GnomAD4 exome AF: 0.0000281 AC: 41AN: 1460228Hom.: 0 Cov.: 32 AF XY: 0.0000262 AC XY: 19AN XY: 726280
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GnomAD4 genome ? AF: 0.000329 AC: 50AN: 152048Hom.: 0 Cov.: 32 AF XY: 0.000323 AC XY: 24AN XY: 74324
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Dec 07, 2023 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 08, 2024 | The c.2851+5G>A intronic alteration consists of a G to A substitution 5 nucleotides after exon 25 of the TRAPPC11 gene. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Dec 09, 2021 | Has not been previously published as pathogenic or benign to our knowledge; In-silico analysis is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown. - |
Autosomal recessive limb-girdle muscular dystrophy type R18 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 25, 2022 | This sequence change falls in intron 25 of the TRAPPC11 gene. It does not directly change the encoded amino acid sequence of the TRAPPC11 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs373713956, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with TRAPPC11-related conditions. ClinVar contains an entry for this variant (Variation ID: 474359). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Calibrated prediction
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dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DL_spliceai
Position offset: -5
Find out detailed SpliceAI scores and Pangolin per-transcript scores at