rs145384040

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr11-119019266-G-A
• chr11-119019266-G-C
• chr11-119019266-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R100L) has been classified as Uncertain significance.

• 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
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with epilepsy, spasticity, and brain atrophy

  Inheritance: AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, ClinGen
• syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016146.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAPPC4	NM_016146.6	MANE Select	c.299G>A	p.Arg100Gln	missense	Exon 2 of 5	NP_057230.1	Q9Y296-1
	TRAPPC4	NM_001318488.2		c.299G>A	p.Arg100Gln	missense	Exon 2 of 5	NP_001305417.1	J3KP27
	TRAPPC4	NM_001318486.2		c.85G>A	p.Gly29Ser	missense	Exon 2 of 4	NP_001305415.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAPPC4	ENST00000533632.6	TSL:1 MANE Select	c.299G>A	p.Arg100Gln	missense	Exon 2 of 5	ENSP00000436005.1	Q9Y296-1
	TRAPPC4	ENST00000533058.5	TSL:2	c.299G>A	p.Arg100Gln	missense	Exon 2 of 5	ENSP00000432920.1	E9PN70
	TRAPPC4	ENST00000359005.8	TSL:2	c.299G>A	p.Arg100Gln	missense	Exon 2 of 5	ENSP00000351896.4	J3KP27

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

African (AFR) AF: 0.00 AC: 0 AN: 41436

American (AMR) AF: 0.0000655 AC: 1 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
MetaSVM	Benign	-0.68	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		6.7
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.20
Sift	Uncertain	0.029	D
Sift4G	Benign	0.12	T
Polyphen		0.97	D
Vest4		0.64
MutPred		0.49		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
Mutation Taster		=34/66	disease causing

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

Other links and lift over

dbSNP: rs145384040; hg19: chr11-118889976;