rs2838473

Positions:

• chr21-44050890-G-A

Variant summary

Our verdict is Benign. Variant got -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

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 Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRAPPC10	NM_003274.5	c.286-1390G>A		intron_variant		ENST00000291574.9	NP_003265.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRAPPC10	ENST00000291574.9	c.286-1390G>A		intron_variant		1	NM_003274.5	ENSP00000291574	P1
TRAPPC10	ENST00000380221.7	c.286-1390G>A		intron_variant		1		ENSP00000369570
TRAPPC10	ENST00000422875.5	c.286-1390G>A		intron_variant, NMD_transcript_variant		1		ENSP00000402221

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

Gnomad4 AFR AF: 0.690

Gnomad4 AMR AF: 0.303

Gnomad4 ASJ AF: 0.293

Gnomad4 EAS AF: 0.294

Gnomad4 SAS AF: 0.416

Gnomad4 FIN AF: 0.163

Gnomad4 NFE AF: 0.200

Gnomad4 OTH AF: 0.313

Alfa AF: 0.292 Hom.: 1110

Bravo AF: 0.376

Asia WGS AF: 0.395 AC: 1370 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.47
DANN	Benign	0.73

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

LitVar

Other links and lift over

dbSNP: rs2838473; hg19: chr21-45470771;