6-116496989-T-C

Variant names:

• chr6-116496989-T-C
• rs1404367221
• NM_001139444.3:c.511A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001139444.3(TRAPPC3L):​c.511A>G​(p.Lys171Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000717 in 1,394,392 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: TRAPPC3L NM_001139444.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.84

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]

ENSG00000234117 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15526745).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAPPC3L	NM_001139444.3	c.511A>G	p.Lys171Glu	missense_variant	Exon 5 of 5	ENST00000368602.4	NP_001132916.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAPPC3L	ENST00000368602.4	c.511A>G	p.Lys171Glu	missense_variant	Exon 5 of 5	5	NM_001139444.3	ENSP00000357591.3
TRAPPC3L	ENST00000437098.5	c.469A>G	p.Lys157Glu	missense_variant	Exon 4 of 4	3		ENSP00000395769.1
TRAPPC3L	ENST00000356128.4	c.259A>G	p.Lys87Glu	missense_variant	Exon 3 of 3	2		ENSP00000348445.4
ENSG00000234117	ENST00000420595.2	n.627T>C		non_coding_transcript_exon_variant	Exon 3 of 3	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.17e-7 AC: 1 AN: 1394392 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 687602

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: 0.0000129

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 18, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.511A>G (p.K171E) alteration is located in exon 5 (coding exon 5) of the TRAPPC3L gene. This alteration results from a A to G substitution at nucleotide position 511, causing the lysine (K) at amino acid position 171 to be replaced by a glutamic acid (E). 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	Benign	0.11
BayesDel_addAF	Benign	-0.048	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.072	.;.;T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.030
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.67	T;T;T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.16	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	.;.;M
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-2.3	N;N;N
REVEL	Benign	0.037
Sift	Benign	0.25	T;T;T
Sift4G	Benign	0.29	T;T;T
Polyphen		0.10	.;.;B
Vest4		0.35
MutPred		0.38		.;.;Loss of MoRF binding (P = 0.0029);
MVP		0.055
ClinPred		0.83	D
GERP RS		4.5
Varity_R		0.36
gMVP		0.41

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: rs1404367221; hg19: chr6-116818152;