11-119020198-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.399C>T(p.Gly133=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00531 in 1,613,946 control chromosomes in the GnomAD database, including 364 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.027 (179 hom., cov: 33)
  • Exomes 𝑓: 0.0030 (185 hom.)
• Consequence: TRAPPC4 NM_016146.6 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.593

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=-0.26).
• BP6: Variant 11-119020198-C-T is Benign according to our data. Variant chr11-119020198-C-T is described in ClinVar as [Benign]. Clinvar id is 1263994.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.593 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0896 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRAPPC4	NM_016146.6	c.399C>T	p.Gly133=	synonymous_variant	3/5	ENST00000533632.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRAPPC4	ENST00000533632.6	c.399C>T	p.Gly133=	synonymous_variant	3/5	1	NM_016146.6	P1

Frequencies

GnomAD3 genomes AF: 0.0270 AC: 4114 AN: 152136 Hom.: 179 Cov.: 33

Gnomad AFR AF: 0.0920

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0143

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000573

Gnomad OTH AF: 0.0191

GnomAD3 exomes AF: 0.00770 AC: 1935 AN: 251220 Hom.: 90 AF XY: 0.00557 AC XY: 757 AN XY: 135804

Gnomad AFR exome AF: 0.0987

Gnomad AMR exome AF: 0.00645

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.000558

Gnomad NFE exome AF: 0.000563

Gnomad OTH exome AF: 0.00457

GnomAD4 exome AF: 0.00304 AC: 4440 AN: 1461692 Hom.: 185 Cov.: 30 AF XY: 0.00262 AC XY: 1904 AN XY: 727158

Gnomad4 AFR exome AF: 0.0918

Gnomad4 AMR exome AF: 0.00736

Gnomad4 ASJ exome AF: 0.000191

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000139

Gnomad4 FIN exome AF: 0.000619

Gnomad4 NFE exome AF: 0.000454

Gnomad4 OTH exome AF: 0.00747

GnomAD4 genome AF: 0.0271 AC: 4128 AN: 152254 Hom.: 179 Cov.: 33 AF XY: 0.0264 AC XY: 1966 AN XY: 74436

Gnomad4 AFR AF: 0.0921

Gnomad4 AMR AF: 0.0143

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000377

Gnomad4 NFE AF: 0.000573

Gnomad4 OTH AF: 0.0189

Alfa AF: 0.0124 Hom.: 39

Bravo AF: 0.0313

Asia WGS AF: 0.00346 AC: 12 AN: 3478

EpiCase AF: 0.000600

EpiControl AF: 0.000711

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
Cadd	Benign	14
Dann	Benign	0.89
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs61730037; hg19: chr11-118890908;