Variant 11-119019245-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_016146.6(TRAPPC4):c.278C>T(p.Pro93Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,186 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: 𝑓 0.0000066 ( 0 hom., cov: 33)

Consequence

TRAPPC4
NM_016146.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter P:1U:1

Conservation

PhyloP100: 7.78

Variant links:

Genes affected

TRAPPC4 (HGNC:19943): (trafficking protein particle complex subunit 4) Involved in autophagy and endoplasmic reticulum to Golgi vesicle-mediated transport. Part of TRAPP complex. [provided by Alliance of Genome Resources, Apr 2022]

TRAPPC4 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.926

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRAPPC4	NM_016146.6 linkuse as main transcript	c.278C>T	p.Pro93Leu	missense_variant	2/5	ENST00000533632.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRAPPC4	ENST00000533632.6 linkuse as main transcript	c.278C>T	p.Pro93Leu	missense_variant	2/5	1	NM_016146.6	P1	Q9Y296-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251466

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135910

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:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Pathogenic:1Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Neurodevelopmental disorder with epilepsy, spasticity, and brain atrophy

Pathogenic:1Uncertain:1

Pathogenic, no assertion criteria provided	literature only	OMIM	Feb 28, 2023	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India	Jan 20, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Uncertain

0.11

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Benign

0.33

T;.;.

Eigen

Pathogenic

0.91

Eigen_PC

Pathogenic

0.88

FATHMM_MKL

Uncertain

0.94

M_CAP

Uncertain

0.087

MetaRNN

Pathogenic

0.93

D;D;D

MetaSVM

Benign

-0.88

MutationAssessor

Uncertain

2.9

M;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Pathogenic

0.83

PROVEAN

Pathogenic

-9.2

D;D;D

REVEL

Uncertain

0.58

Sift

Uncertain

0.0010

D;D;D

Sift4G

Uncertain

0.0020

D;D;D

Polyphen

1.0

D;.;.

Vest4

0.91

MutPred

0.77

Loss of catalytic residue at N91 (P = 0.0517);Loss of catalytic residue at N91 (P = 0.0517);Loss of catalytic residue at N91 (P = 0.0517);

MVP

0.66

MPC

1.4

ClinPred

1.0

GERP RS

5.6

Varity_R

0.85

gMVP

0.92

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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