21-44012507-A-C

Variant names:

• chr21-44012507-A-C
• rs1051415355
• NM_003274.5:c.14A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003274.5(TRAPPC10):​c.14A>C​(p.Glu5Ala) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E5G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRAPPC10 NM_003274.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.74
• Publications: 0 publications found

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

ACMG classification

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=0.12139252).

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>C	p.Glu5Ala	missense	Exon 1 of 23	NP_003265.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAPPC10	ENST00000291574.9	TSL:1 MANE Select	c.14A>C	p.Glu5Ala	missense	Exon 1 of 23	ENSP00000291574.4	P48553-1
	TRAPPC10	ENST00000380221.7	TSL:1	c.14A>C	p.Glu5Ala	missense	Exon 1 of 7	ENSP00000369570.3	P48553-2
	TRAPPC10	ENST00000422875.5	TSL:1	n.14A>C		non_coding_transcript_exon	Exon 1 of 24	ENSP00000402221.1	F8WE24

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.62	T
M_CAP	Uncertain	0.24	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		2.7
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-0.44	N
REVEL	Benign	0.038
Sift	Benign	0.11	T
Sift4G	Uncertain	0.044	D
Polyphen		0.0	B
Vest4		0.23
MutPred		0.15		Loss of disorder (P = 0.0794)
MVP		0.068
MPC		0.28
ClinPred		0.30	T
GERP RS		2.4
PromoterAI		-0.031	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.072
gMVP		0.33
Mutation Taster		=78/22	polymorphism

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

Other links and lift over

dbSNP: rs1051415355; hg19: chr21-45432388;