6-116500501-T-A

Position:

• chr6-116500501-T-A

Variant summary

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

The NM_001139444.3(TRAPPC3L):​c.406A>T​(p.Ile136Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000858 in 1,398,302 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000086 (0 hom.)
• Consequence: TRAPPC3L NM_001139444.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.43

Genes affected

TRAPPC3L (HGNC:21090): (trafficking protein particle complex subunit 3L) Predicted to be involved in endoplasmic reticulum to Golgi vesicle-mediated transport and intra-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/exons	MANE	Protein	UniProt
TRAPPC3L	NM_001139444.3	c.406A>T	p.Ile136Phe	missense_variant	4/5	ENST00000368602.4	NP_001132916.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRAPPC3L	ENST00000368602.4	c.406A>T	p.Ile136Phe	missense_variant	4/5	5	NM_001139444.3	ENSP00000357591.3
TRAPPC3L	ENST00000437098.5	c.364A>T	p.Ile122Phe	missense_variant	3/4	3		ENSP00000395769.1
TRAPPC3L	ENST00000356128.4	c.154A>T	p.Ile52Phe	missense_variant	2/3	2		ENSP00000348445.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000858 AC: 12 AN: 1398302 Hom.: 0 Cov.: 31 AF XY: 0.00000580 AC XY: 4 AN XY: 689642

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000111

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 26, 2024

The c.406A>T (p.I136F) alteration is located in exon 4 (coding exon 4) of the TRAPPC3L gene. This alteration results from a A to T substitution at nucleotide position 406, causing the isoleucine (I) at amino acid position 136 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.34	.;.;T
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.83	T;T;T
M_CAP	Benign	0.068	D
MetaRNN	Uncertain	0.72	D;D;D
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Pathogenic	3.0	.;.;M
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-3.1	D;D;D
REVEL	Uncertain	0.43
Sift	Uncertain	0.0030	D;D;D
Sift4G	Uncertain	0.0060	D;D;D
Polyphen		0.99	.;.;D
Vest4		0.76
MutPred		0.70		.;.;Gain of methylation at R137 (P = 0.0877);
MVP		0.22
ClinPred		0.99	D
GERP RS		5.6
Varity_R		0.69
gMVP		0.76

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-116821664;