6-116500654-T-C

Variant names:

• chr6-116500654-T-C
• NM_001139444.3:c.253A>G

Variant summary

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

The NM_001139444.3(TRAPPC3L):​c.253A>G​(p.Met85Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TRAPPC3L NM_001139444.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.91

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 rank	MANE	Protein	UniProt
TRAPPC3L	NM_001139444.3	c.253A>G	p.Met85Val	missense_variant	Exon 4 of 5	ENST00000368602.4	NP_001132916.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAPPC3L	ENST00000368602.4	c.253A>G	p.Met85Val	missense_variant	Exon 4 of 5	5	NM_001139444.3	ENSP00000357591.3
TRAPPC3L	ENST00000356128.4	c.1A>G	p.Met1?	start_lost	Exon 2 of 3	2		ENSP00000348445.4
TRAPPC3L	ENST00000437098.5	c.211A>G	p.Met71Val	missense_variant	Exon 3 of 4	3		ENSP00000395769.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 31, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.253A>G (p.M85V) alteration is located in exon 4 (coding exon 4) of the TRAPPC3L gene. This alteration results from a A to G substitution at nucleotide position 253, causing the methionine (M) at amino acid position 85 to be replaced by a valine (V). 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	0.18
BayesDel_addAF	Uncertain	0.060	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.10	.;.;T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D;D;D
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.67	D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	.;.;M
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-2.1	N;N;N
REVEL	Benign	0.18
Sift	Benign	0.084	T;T;T
Sift4G	Uncertain	0.047	D;T;T
Polyphen		0.82	.;.;P
Vest4		0.73
MutPred		0.56		.;.;Gain of methylation at K84 (P = 0.0219);
MVP		0.20
ClinPred		0.91	D
GERP RS		5.4
Varity_R		0.59
gMVP		0.56

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-116821817;