21-44052388-G-A

Position:

• chr21-44052388-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003274.5(TRAPPC10):​c.394G>A​(p.Ala132Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 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)
• Consequence: TRAPPC10 NM_003274.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.32

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=0.10252941).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRAPPC10	NM_003274.5	c.394G>A	p.Ala132Thr	missense_variant	4/23	ENST00000291574.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRAPPC10	ENST00000291574.9	c.394G>A	p.Ala132Thr	missense_variant	4/23	1	NM_003274.5	P1
TRAPPC10	ENST00000380221.7	c.394G>A	p.Ala132Thr	missense_variant	4/7	1
TRAPPC10	ENST00000422875.5	c.394G>A	p.Ala132Thr	missense_variant, NMD_transcript_variant	4/24	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 02, 2022

The c.394G>A (p.A132T) alteration is located in exon 4 (coding exon 4) of the TRAPPC10 gene. This alteration results from a G to A substitution at nucleotide position 394, causing the alanine (A) at amino acid position 132 to be replaced by a threonine (T). 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	Benign	0.068
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	23
DANN	Benign	0.68
Eigen	Benign	-0.023
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.76	N;N
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.87	N;N
REVEL	Benign	0.069
Sift	Benign	0.63	T;T
Sift4G	Benign	0.39	T;T
Polyphen		0.084	.;B
Vest4		0.14
MutPred		0.32		Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);
MVP		0.043
MPC		0.27
ClinPred		0.93	D
GERP RS		4.9
Varity_R		0.13
gMVP		0.32

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: chr21-45472269;