11-119019312-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_016146.6(TRAPPC4):c.345C>T(p.Phe115=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0949 in 1,612,310 control chromosomes in the GnomAD database, including 8,540 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.085 (669 hom., cov: 32)
  • Exomes 𝑓: 0.096 (7871 hom.)
• Consequence: TRAPPC4 NM_016146.6 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.04

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BP6: Variant 11-119019312-C-T is Benign according to our data. Variant chr11-119019312-C-T is described in ClinVar as [Benign]. Clinvar id is 1275542.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.04 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRAPPC4	NM_016146.6	c.345C>T	p.Phe115=	synonymous_variant	2/5	ENST00000533632.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRAPPC4	ENST00000533632.6	c.345C>T	p.Phe115=	synonymous_variant	2/5	1	NM_016146.6	P1

Frequencies

GnomAD3 genomes AF: 0.0848 AC: 12893 AN: 152078 Hom.: 667 Cov.: 32

Gnomad AFR AF: 0.0696

Gnomad AMI AF: 0.0978

Gnomad AMR AF: 0.0586

Gnomad ASJ AF: 0.0325

Gnomad EAS AF: 0.0779

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0838

Gnomad OTH AF: 0.0653

GnomAD3 exomes AF: 0.0999 AC: 25052 AN: 250734 Hom.: 1696 AF XY: 0.108 AC XY: 14578 AN XY: 135478

Gnomad AFR exome AF: 0.0719

Gnomad AMR exome AF: 0.0625

Gnomad ASJ exome AF: 0.0402

Gnomad EAS exome AF: 0.0792

Gnomad SAS exome AF: 0.220

Gnomad FIN exome AF: 0.142

Gnomad NFE exome AF: 0.0846

Gnomad OTH exome AF: 0.0781

GnomAD4 exome AF: 0.0959 AC: 140023 AN: 1460114 Hom.: 7871 Cov.: 33 AF XY: 0.0995 AC XY: 72223 AN XY: 726028

Gnomad4 AFR exome AF: 0.0668

Gnomad4 AMR exome AF: 0.0622

Gnomad4 ASJ exome AF: 0.0399

Gnomad4 EAS exome AF: 0.0959

Gnomad4 SAS exome AF: 0.220

Gnomad4 FIN exome AF: 0.137

Gnomad4 NFE exome AF: 0.0881

Gnomad4 OTH exome AF: 0.0915

GnomAD4 genome AF: 0.0848 AC: 12905 AN: 152196 Hom.: 669 Cov.: 32 AF XY: 0.0889 AC XY: 6616 AN XY: 74418

Gnomad4 AFR AF: 0.0696

Gnomad4 AMR AF: 0.0585

Gnomad4 ASJ AF: 0.0325

Gnomad4 EAS AF: 0.0781

Gnomad4 SAS AF: 0.233

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.0838

Gnomad4 OTH AF: 0.0693

Alfa AF: 0.0792 Hom.: 478

Bravo AF: 0.0740

Asia WGS AF: 0.161 AC: 561 AN: 3478

EpiCase AF: 0.0823

EpiControl AF: 0.0852

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
Cadd	Benign	13
Dann	Benign	0.95
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs3802881; hg19: chr11-118890022;