14-39150354-A-G

Position:

• chr14-39150354-A-G

Variant summary

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

The NM_001079537.2(TRAPPC6B):​c.473T>C​(p.Leu158Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000418 in 1,433,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000042 (0 hom.)
• Consequence: TRAPPC6B NM_001079537.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.12

Genes affected

TRAPPC6B (HGNC:23066): (trafficking protein particle complex subunit 6B) TRAPPC6B is a component of TRAPP complexes, which are tethering complexes involved in vesicle transport (Kummel et al., 2005 [PubMed 16025134]).[supplied by OMIM, Mar 2008]

TRAPPC6B (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=0.23421437).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRAPPC6B	NM_001079537.2	c.473T>C	p.Leu158Pro	missense_variant	6/6	ENST00000330149.10	NP_001073005.1
TRAPPC6B	NM_177452.4	c.389T>C	p.Leu130Pro	missense_variant	5/5		NP_803235.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRAPPC6B	ENST00000330149.10	c.473T>C	p.Leu158Pro	missense_variant	6/6	1	NM_001079537.2	ENSP00000330289.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000418 AC: 6 AN: 1433862 Hom.: 0 Cov.: 28 AF XY: 0.00000281 AC XY: 2 AN XY: 712890

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: 0.00000543

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 09, 2024

The c.473T>C (p.L158P) alteration is located in exon 6 (coding exon 6) of the TRAPPC6B gene. This alteration results from a T to C substitution at nucleotide position 473, causing the leucine (L) at amino acid position 158 to be replaced by a proline (P). 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	0.53
BayesDel_addAF	Uncertain	0.035	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.028	T;.
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.87	D;D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-0.59	T
MutationAssessor	Benign	0.90	L;.
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.87	N;N
REVEL	Benign	0.24
Sift	Uncertain	0.0030	D;D
Sift4G	Uncertain	0.0080	D;D
Polyphen		0.48	P;P
Vest4		0.42
MutPred		0.52		Loss of stability (P = 0.0047);.;
MVP		0.41
MPC		0.86
ClinPred		0.87	D
GERP RS		4.5
Varity_R		0.48
gMVP		0.40

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: chr14-39619558;