chr21-44075088-A-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_003274.5(TRAPPC10):c.1235A>T(p.Asn412Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000985 in 1,614,152 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000099 ( 1 hom., cov: 32)
Exomes 𝑓: 0.000099 ( 0 hom. )
Consequence
TRAPPC10
NM_003274.5 missense
NM_003274.5 missense
Scores
6
13
Clinical Significance
Conservation
PhyloP100: 3.61
Genes affected
TRAPPC10 (HGNC:11868): (trafficking protein particle complex subunit 10) The protein encoded by this gene is a transmembrane protein found in the cis-Golgi complex. The encoded protein is part of the multisubunit transport protein particle (TRAPP) complex and may be involved in vesicular transport from the endoplasmic reticulum to the Golgi. Mutations in this gene could be responsible for the Unverricht-Lundborg type of progressive myoclonus epilepsy, or for autoimmune polyglandular disease type 1. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.1355699).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRAPPC10 | NM_003274.5 | c.1235A>T | p.Asn412Ile | missense_variant | 9/23 | ENST00000291574.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRAPPC10 | ENST00000291574.9 | c.1235A>T | p.Asn412Ile | missense_variant | 9/23 | 1 | NM_003274.5 | P1 | |
TRAPPC10 | ENST00000422875.5 | c.*553A>T | 3_prime_UTR_variant, NMD_transcript_variant | 10/24 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000986 AC: 15AN: 152162Hom.: 1 Cov.: 32
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.0000676 AC: 17AN: 251476Hom.: 0 AF XY: 0.0000809 AC XY: 11AN XY: 135910
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GnomAD4 exome AF: 0.0000985 AC: 144AN: 1461872Hom.: 0 Cov.: 30 AF XY: 0.0000935 AC XY: 68AN XY: 727236
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GnomAD4 genome ? AF: 0.0000985 AC: 15AN: 152280Hom.: 1 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74462
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 25, 2022 | The c.1235A>T (p.N412I) alteration is located in exon 9 (coding exon 9) of the TRAPPC10 gene. This alteration results from a A to T substitution at nucleotide position 1235, causing the asparagine (N) at amino acid position 412 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
N
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Uncertain
D
Sift4G
Uncertain
T
Polyphen
P
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at