NM_016146.6:c.299G>A

Variant names:

• chr11-119019266-G-A
• rs145384040
• NM_016146.6:c.299G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016146.6(TRAPPC4):​c.299G>A​(p.Arg100Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,148 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: TRAPPC4 NM_016146.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.74

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAPPC4	NM_016146.6	c.299G>A	p.Arg100Gln	missense_variant	Exon 2 of 5	ENST00000533632.6	NP_057230.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAPPC4	ENST00000533632.6	c.299G>A	p.Arg100Gln	missense_variant	Exon 2 of 5	1	NM_016146.6	ENSP00000436005.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152148 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152148 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74328

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000655

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Uncertain	0.088	D
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	31
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.14	T;.;.
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Uncertain	0.96	D
M_CAP	Benign	0.035	D
MetaRNN	Uncertain	0.67	D;D;D
MetaSVM	Benign	-0.68	T
MutationAssessor	Uncertain	2.3	M;.;.
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-3.0	D;D;D
REVEL	Benign	0.20
Sift	Uncertain	0.029	D;D;D
Sift4G	Benign	0.12	T;T;T
Polyphen		0.97	D;.;.
Vest4		0.64
MutPred		0.49		Loss of methylation at R100 (P = 0.0536);Loss of methylation at R100 (P = 0.0536);Loss of methylation at R100 (P = 0.0536);
MVP		0.67
MPC		1.4
ClinPred		0.99	D
GERP RS		5.6
Varity_R		0.94
gMVP		0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs145384040; hg19: chr11-118889976;