Genetic Variant TRAPPC10:p.Glu5Gly (chr21-44012507-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003274.5(TRAPPC10):c.14A>G(p.Glu5Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TRAPPC10
NM_003274.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.74

Publications

0 publications found

Variant links:

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]

TRAPPC10 Gene-Disease associations (from GenCC):

neurodevelopmental disorder with microcephaly, short stature, and speech delay
Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, PanelApp Australia

TRAPPC10 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12481406).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003274.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAPPC10	NM_003274.5	MANE Select	c.14A>G	p.Glu5Gly	missense	Exon 1 of 23	NP_003265.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRAPPC10	ENST00000291574.9	TSL:1 MANE Select	c.14A>G	p.Glu5Gly	missense	Exon 1 of 23	ENSP00000291574.4	P48553-1
TRAPPC10	ENST00000380221.7	TSL:1	c.14A>G	p.Glu5Gly	missense	Exon 1 of 7	ENSP00000369570.3	P48553-2
TRAPPC10	ENST00000422875.5	TSL:1	n.14A>G		non_coding_transcript_exon	Exon 1 of 24	ENSP00000402221.1	F8WE24

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1377302

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

679620

African (AFR)

AF:

0.00

AC:

AN:

29992

American (AMR)

AF:

0.00

AC:

AN:

34660

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24388

East Asian (EAS)

AF:

0.00

AC:

AN:

34478

South Asian (SAS)

AF:

0.00

AC:

AN:

78068

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47184

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4060

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1067910

Other (OTH)

AF:

0.00

AC:

AN:

56562

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Neurodevelopmental disorder with microcephaly, short stature, and speech delay (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.059

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.014

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.42

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.55

M_CAP

Pathogenic

0.32

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.41

PhyloP100

2.7

PrimateAI

Uncertain

0.77

PROVEAN

Benign

0.030

REVEL

Benign

0.048

Sift

Uncertain

0.018

Sift4G

Uncertain

0.018

Polyphen

0.018

Vest4

0.20

MutPred

0.13

Loss of solvent accessibility (P = 0.0769)

MVP

0.068

MPC

0.31

ClinPred

0.53

GERP RS

2.4

PromoterAI

-0.073

Neutral

(source)

Varity_R

0.084

gMVP

0.29

Mutation Taster

=80/20

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over