Variant chr21-44032177-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_003274.5(TRAPPC10):c.149+5G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.001 in 1,611,586 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00059 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 3 hom. )

Consequence

TRAPPC10
NM_003274.5 splice_region, intron

Scores

Splicing: ADA: 0.3840

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.08

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 21-44032177-G-C is Benign according to our data. Variant chr21-44032177-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 3034396.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRAPPC10	NM_003274.5 linkuse as main transcript	c.149+5G>C		splice_region_variant, intron_variant		ENST00000291574.9	NP_003265.3	P48553-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
TRAPPC10	ENST00000291574.9 linkuse as main transcript	c.149+5G>C	splice_region_variant, intron_variant	1	NM_003274.5	ENSP00000291574.4	P48553-1
TRAPPC10	ENST00000380221.7 linkuse as main transcript	c.149+5G>C	splice_region_variant, intron_variant	1		ENSP00000369570.3	P48553-2
TRAPPC10	ENST00000422875.5 linkuse as main transcript	n.149+5G>C	splice_region_variant, intron_variant	1		ENSP00000402221.1	F8WE24

Frequencies

GnomAD3 genomes

AF:

0.000592

AC:

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000721

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000945

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00100

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000638

AC:

159

AN:

249298

Hom.:

AF XY:

0.000594

AC XY:

AN XY:

134682

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.00123

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000947

Gnomad OTH exome

AF:

0.00115

GnomAD4 exome

AF:

0.00104

AC:

1521

AN:

1459350

Hom.:

Cov.:

AF XY:

0.000984

AC XY:

714

AN XY:

725896

show subpopulations

Gnomad4 AFR exome

AF:

0.000180

Gnomad4 AMR exome

AF:

0.00104

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00124

Gnomad4 OTH exome

AF:

0.00139

GnomAD4 genome

AF:

0.000591

AC:

AN:

152236

Hom.:

Cov.:

AF XY:

0.000524

AC XY:

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.000720

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000945

Gnomad4 NFE

AF:

0.00100

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000958

Hom.:

Bravo

AF:

0.000650

EpiCase

AF:

0.00109

EpiControl

AF:

0.000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

TRAPPC10-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 20, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

DANN

Benign

0.55

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.38

dbscSNV1_RF

Benign

0.43

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over