21-44012507-AG-GT

Variant names:

• chr21-44012507-AG-GT
• NM_003274.5:c.14_15delAGinsGT
• TRAPPC10 p.Glu5Gly

Variant summary

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

The NM_003274.5(TRAPPC10):​c.14_15delAGinsGT​(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. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• 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: Ambry Genetics, G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)

ACMG classification

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

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.14_15delAGinsGT	p.Glu5Gly	missense	N/A	NP_003265.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAPPC10	ENST00000291574.9	TSL:1 MANE Select	c.14_15delAGinsGT	p.Glu5Gly	missense	N/A	ENSP00000291574.4	P48553-1
	TRAPPC10	ENST00000380221.7	TSL:1	c.14_15delAGinsGT	p.Glu5Gly	missense	N/A	ENSP00000369570.3	P48553-2
	TRAPPC10	ENST00000422875.5	TSL:1	n.14_15delAGinsGT		non_coding_transcript_exon	Exon 1 of 24	ENSP00000402221.1	F8WE24

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr21-45432388;