11-119019375-C-T

Position:

• chr11-119019375-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001318492.2(TRAPPC4):​c.-15C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 1,553,262 control chromosomes in the GnomAD database, including 12,767 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1027 hom., cov: 32)
  • Exomes 𝑓: 0.13 (11740 hom.)
• Consequence: TRAPPC4 NM_001318492.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0630

Genes affected

TRAPPC4 (HGNC:19943): (trafficking protein particle complex subunit 4) Involved in autophagy and endoplasmic reticulum to Golgi vesicle-mediated transport. Part of TRAPP complex. [provided by Alliance of Genome Resources, Apr 2022]

TRAPPC4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 11-119019375-C-T is Benign according to our data. Variant chr11-119019375-C-T is described in ClinVar as [Benign]. Clinvar id is 1289468.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRAPPC4	NM_016146.6	c.350+58C>T		intron_variant		ENST00000533632.6	NP_057230.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRAPPC4	ENST00000533632.6	c.350+58C>T		intron_variant		1	NM_016146.6	ENSP00000436005.1

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16511 AN: 152114 Hom.: 1028 Cov.: 32

Gnomad AFR AF: 0.0710

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.0127

Gnomad SAS AF: 0.0900

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.138

GnomAD4 exome AF: 0.126 AC: 177086 AN: 1401030 Hom.: 11740 Cov.: 24 AF XY: 0.126 AC XY: 87370 AN XY: 693926

Gnomad4 AFR exome AF: 0.0713

Gnomad4 AMR exome AF: 0.0960

Gnomad4 ASJ exome AF: 0.150

Gnomad4 EAS exome AF: 0.0189

Gnomad4 SAS exome AF: 0.0907

Gnomad4 FIN exome AF: 0.101

Gnomad4 NFE exome AF: 0.136

Gnomad4 OTH exome AF: 0.129

GnomAD4 genome AF: 0.108 AC: 16513 AN: 152232 Hom.: 1027 Cov.: 32 AF XY: 0.105 AC XY: 7851 AN XY: 74432

Gnomad4 AFR AF: 0.0710

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.141

Gnomad4 EAS AF: 0.0127

Gnomad4 SAS AF: 0.0898

Gnomad4 FIN AF: 0.104

Gnomad4 NFE AF: 0.134

Gnomad4 OTH AF: 0.137

Alfa AF: 0.126 Hom.: 1618

Bravo AF: 0.109

Asia WGS AF: 0.0610 AC: 212 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 15, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.8
DANN	Benign	0.90

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: rs4938619; hg19: chr11-118890085;