17-7931546-A-G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_021210.5(TRAPPC1):ā€‹c.130T>Cā€‹(p.Ser44Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,580 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 30)
Exomes š‘“: 0.0000034 ( 0 hom. )

Consequence

TRAPPC1
NM_021210.5 missense

Scores

11
6
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.23
Variant links:
Genes affected
TRAPPC1 (HGNC:19894): (trafficking protein particle complex subunit 1) This gene product plays a role in vesicular transport of proteins to the Golgi apparatus from the endoplasmic reticulum. The encoded protein is a component of the multisubunit transport protein particle (TRAPP) complex. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Oct 2009]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.982

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TRAPPC1NM_021210.5 linkc.130T>C p.Ser44Pro missense_variant 2/4 ENST00000303731.9 NP_067033.1 Q9Y5R8
TRAPPC1NM_001166621.1 linkc.130T>C p.Ser44Pro missense_variant 3/5 NP_001160093.1 Q9Y5R8
TRAPPC1NR_030684.2 linkn.216+185T>C intron_variant
TRAPPC1NR_030697.1 linkn.159+185T>C intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TRAPPC1ENST00000303731.9 linkc.130T>C p.Ser44Pro missense_variant 2/41 NM_021210.5 ENSP00000302783.4 Q9Y5R8

Frequencies

GnomAD3 genomes
Cov.:
30
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251458
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135896
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1461580
Hom.:
0
Cov.:
33
AF XY:
0.00000413
AC XY:
3
AN XY:
727094
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
30

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 submitterclinical testingAmbry GeneticsAug 22, 2023The c.130T>C (p.S44P) alteration is located in exon 2 (coding exon 2) of the TRAPPC1 gene. This alteration results from a T to C substitution at nucleotide position 130, causing the serine (S) at amino acid position 44 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
1.0
BayesDel_addAF
Pathogenic
0.41
D
BayesDel_noAF
Pathogenic
0.44
CADD
Pathogenic
33
DANN
Uncertain
1.0
DEOGEN2
Benign
0.26
T;T;.;T
Eigen
Pathogenic
0.95
Eigen_PC
Pathogenic
0.89
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.95
D;.;D;D
M_CAP
Pathogenic
0.31
D
MetaRNN
Pathogenic
0.98
D;D;D;D
MetaSVM
Pathogenic
0.89
D
MutationAssessor
Pathogenic
3.4
M;M;.;.
PrimateAI
Uncertain
0.77
T
PROVEAN
Pathogenic
-4.8
D;D;.;.
REVEL
Pathogenic
0.95
Sift
Uncertain
0.0010
D;D;.;.
Sift4G
Uncertain
0.0050
D;D;D;D
Polyphen
1.0
D;D;.;.
Vest4
0.97
MutPred
0.91
Loss of catalytic residue at S44 (P = 0.0194);Loss of catalytic residue at S44 (P = 0.0194);Loss of catalytic residue at S44 (P = 0.0194);Loss of catalytic residue at S44 (P = 0.0194);
MVP
0.96
MPC
2.1
ClinPred
0.99
D
GERP RS
5.7
Varity_R
0.94
gMVP
0.96

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1417305377; hg19: chr17-7834864; API