chr21-44080879-A-T

Variant names:

• chr21-44080879-A-T
• rs13052277
• NM_003274.5:c.1723+752A>T

Variant summary

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

The NM_003274.5(TRAPPC10):​c.1723+752A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 123,754 control chromosomes in the GnomAD database, including 3,866 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 0.25 (3866 hom., cov: 27)
• Consequence: TRAPPC10 NM_003274.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.473
• Publications: 2 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.511 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.1723+752A>T		intron	N/A	NP_003265.3
	TRAPPC10	NM_001351709.1		c.322+752A>T		intron	N/A	NP_001338638.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAPPC10	ENST00000291574.9	TSL:1 MANE Select	c.1723+752A>T		intron	N/A	ENSP00000291574.4
	TRAPPC10	ENST00000422875.5	TSL:1	n.*1041+752A>T		intron	N/A	ENSP00000402221.1
	TRAPPC10	ENST00000915074.1		c.1813+752A>T		intron	N/A	ENSP00000585133.1

Frequencies

GnomAD3 genomes AF: 0.248 AC: 30663 AN: 123702 Hom.: 3848 Cov.: 27

Gnomad AFR AF: 0.517

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.237

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.217

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.232

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

GnomAD4 genome AF: 0.248 AC: 30715 AN: 123754 Hom.: 3866 Cov.: 27 AF XY: 0.248 AC XY: 14964 AN XY: 60408

African (AFR) AF: 0.518 AC: 14169 AN: 27364

American (AMR) AF: 0.215 AC: 2629 AN: 12224

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 806 AN: 3116

East Asian (EAS) AF: 0.237 AC: 1036 AN: 4368

South Asian (SAS) AF: 0.327 AC: 1226 AN: 3748

European-Finnish (FIN) AF: 0.123 AC: 1114 AN: 9034

Middle Eastern (MID) AF: 0.225 AC: 53 AN: 236

European-Non Finnish (NFE) AF: 0.148 AC: 9058 AN: 61090

Other (OTH) AF: 0.241 AC: 411 AN: 1708

Alfa AF: 0.205 Hom.: 285

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.17
DANN	Benign	0.24
PhyloP100		-0.47
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: rs13052277; hg19: chr21-45500760; COSMIC: COSV52377271;