Variant 17-7931546-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_021210.5(TRAPPC1):c.130T>C(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 (★).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

TRAPPC1
NM_021210.5 missense

Scores

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]

TRAPPC1 links:

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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
TRAPPC1	NM_021210.5 link	c.130T>C	p.Ser44Pro	missense_variant	2/4	ENST00000303731.9	NP_067033.1	Q9Y5R8
TRAPPC1	NM_001166621.1 link	c.130T>C	p.Ser44Pro	missense_variant	3/5		NP_001160093.1	Q9Y5R8
TRAPPC1	NR_030684.2 link	n.216+185T>C		intron_variant
TRAPPC1	NR_030697.1 link	n.159+185T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRAPPC1	ENST00000303731.9 link	c.130T>C	p.Ser44Pro	missense_variant	2/4	1	NM_021210.5	ENSP00000302783.4		Q9Y5R8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251458

Hom.:

AF XY:

0.00000736

AC XY:

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:

AN:

1461580

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

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.:

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

Aug 22, 2023

The 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

BayesDel_noAF

Pathogenic

0.44

CADD

Pathogenic

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

LIST_S2

Uncertain

0.95

D;.;D;D

M_CAP

Pathogenic

0.31

MetaRNN

Pathogenic

0.98

D;D;D;D

MetaSVM

Pathogenic

0.89

MutationAssessor

Pathogenic

3.4

M;M;.;.

PrimateAI

Uncertain

0.77

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over