rs886041053
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3PP5_Moderate
The NM_021942.6(TRAPPC11):c.1893+3A>G variant causes a splice donor region, intron change. The variant allele was found at a frequency of 0.00000616 in 1,461,534 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 Pathogenic (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000062 ( 0 hom. )
Consequence
TRAPPC11
NM_021942.6 splice_donor_region, intron
NM_021942.6 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.9974
2
Clinical Significance
Conservation
PhyloP100: 6.97
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 5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.
PP5
?
Variant 4-183686751-A-G is Pathogenic according to our data. Variant chr4-183686751-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 268055.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-183686751-A-G is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRAPPC11 | NM_021942.6 | c.1893+3A>G | splice_donor_region_variant, intron_variant | ENST00000334690.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRAPPC11 | ENST00000334690.11 | c.1893+3A>G | splice_donor_region_variant, intron_variant | 1 | NM_021942.6 | P1 | |||
TRAPPC11 | ENST00000357207.8 | c.1893+3A>G | splice_donor_region_variant, intron_variant | 1 | |||||
TRAPPC11 | ENST00000512476.1 | c.711+3A>G | splice_donor_region_variant, intron_variant | 1 | |||||
TRAPPC11 | ENST00000505676.5 | c.*7+3A>G | splice_donor_region_variant, intron_variant, NMD_transcript_variant | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461534Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7AN XY: 727096
GnomAD4 exome
AF:
AC:
9
AN:
1461534
Hom.:
Cov.:
31
AF XY:
AC XY:
7
AN XY:
727096
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Autosomal recessive limb-girdle muscular dystrophy type R18 Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Mar 05, 2020 | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 25, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DL_spliceai
Position offset: -3
Find out detailed SpliceAI scores and Pangolin per-transcript scores at