chr21-44012507-A-G

Position:

• chr21-44012507-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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. 12/21 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.74

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]

ACMG classification

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=0.12481406).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRAPPC10	NM_003274.5	c.14A>G	p.Glu5Gly	missense_variant	1/23	ENST00000291574.9	NP_003265.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRAPPC10	ENST00000291574.9	c.14A>G	p.Glu5Gly	missense_variant	1/23	1	NM_003274.5	ENSP00000291574.4
TRAPPC10	ENST00000380221.7	c.14A>G	p.Glu5Gly	missense_variant	1/7	1		ENSP00000369570.3
TRAPPC10	ENST00000422875.5	n.14A>G		non_coding_transcript_exon_variant	1/24	1		ENSP00000402221.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1377302 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 679620

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Neurodevelopmental disorder with microcephaly, short stature, and speech delay Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Neuberg Centre For Genomic Medicine, NCGM

-

The missense variant c.14A>G (p.Glu5Gly) in TRAPPC10 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Glu5Gly variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes. This variant has not been reported to the ClinVar database. The amino acid Glu at position 5 is changed to a Gly changing protein sequence and it might alter its composition and physico-chemical properties. The amino acid change p.Glu5Gly in TRAPPC10 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance (VUS). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.059	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.014	.;T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.55	T;T
M_CAP	Pathogenic	0.32	D
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.41	N;N
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	0.030	N;N
REVEL	Benign	0.048
Sift	Uncertain	0.018	D;D
Sift4G	Uncertain	0.018	D;D
Polyphen		0.018	.;B
Vest4		0.20
MutPred		0.13		Loss of solvent accessibility (P = 0.0769);Loss of solvent accessibility (P = 0.0769);
MVP		0.068
MPC		0.31
ClinPred		0.53	D
GERP RS		2.4
Varity_R		0.084
gMVP		0.29

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr21-45432388;