rs2838473

Variant names:

• chr21-44050890-G-A
• rs2838473
• NM_003274.5:c.286-1390G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003274.5(TRAPPC10):​c.286-1390G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 152,100 control chromosomes in the GnomAD database, including 13,037 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.36 (13037 hom., cov: 32)
• Consequence: TRAPPC10 NM_003274.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41
• Publications: 4 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, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAPPC10	NM_003274.5	MANE Select	c.286-1390G>A		intron	N/A	NP_003265.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAPPC10	ENST00000291574.9	TSL:1 MANE Select	c.286-1390G>A		intron	N/A	ENSP00000291574.4
	TRAPPC10	ENST00000380221.7	TSL:1	c.286-1390G>A		intron	N/A	ENSP00000369570.3
	TRAPPC10	ENST00000422875.5	TSL:1	n.286-1390G>A		intron	N/A	ENSP00000402221.1

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53928 AN: 151982 Hom.: 12986 Cov.: 32

Gnomad AFR AF: 0.690

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.306

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

GnomAD4 genome AF: 0.355 AC: 54045 AN: 152100 Hom.: 13037 Cov.: 32 AF XY: 0.354 AC XY: 26359 AN XY: 74364

African (AFR) AF: 0.690 AC: 28642 AN: 41504

American (AMR) AF: 0.303 AC: 4630 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1013 AN: 3462

East Asian (EAS) AF: 0.294 AC: 1524 AN: 5176

South Asian (SAS) AF: 0.416 AC: 2008 AN: 4822

European-Finnish (FIN) AF: 0.163 AC: 1724 AN: 10590

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.200 AC: 13593 AN: 67964

Other (OTH) AF: 0.313 AC: 660 AN: 2108

Alfa AF: 0.307 Hom.: 1291

Bravo AF: 0.376

Asia WGS AF: 0.395 AC: 1370 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.47
DANN	Benign	0.73
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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: rs2838473; hg19: chr21-45470771;