rs6767

chr2-3479434-C-Achr2-3479434-C-Gchr2-3479434-C-T

Variant summary

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

The NM_016030.6(TRAPPC12):c.2181C>A(p.Phe727Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. F727F) has been classified as Benign.

• Frequency: Genomes: not found (cov: 34)
• Consequence: TRAPPC12 NM_016030.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.602

Genes affected

TRAPPC12 (HGNC:24284): (trafficking protein particle complex subunit 12) Involved in several processes, including endoplasmic reticulum to Golgi vesicle-mediated transport; positive regulation of protein localization to kinetochore; and regulation of kinetochore assembly. Located in Golgi apparatus; kinetochore; and nucleoplasm. Part of TRAPP complex. Colocalizes with endoplasmic reticulum-Golgi intermediate compartment and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TRAPPC12-AS1 (HGNC:):

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	UniProt
TRAPPC12	NM_016030.6	c.2181C>A	p.Phe727Leu	missense_variant	12/12	ENST00000324266.10
TRAPPC12-AS1	NR_046720.1	n.3560G>T		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRAPPC12	ENST00000324266.10	c.2181C>A	p.Phe727Leu	missense_variant	12/12	1	NM_016030.6	P1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 52

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
Cadd	Benign	18
Dann	Uncertain	0.99
DEOGEN2	Benign	0.025	T;T;T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.50
FATHMM_MKL	Uncertain	0.94	D
M_CAP	Benign	0.057	D
MetaRNN	Uncertain	0.64	D;D;D
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	1.4	L;L;.
MutationTaster	Benign	0.000017	P;P
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-2.7	D;D;D
REVEL	Uncertain	0.32
Sift	Benign	0.18	T;T;D
Sift4G	Benign	0.35	T;T;D
Polyphen		0.93	P;P;.
Vest4		0.77
MutPred		0.36		Gain of disorder (P = 0.0436);Gain of disorder (P = 0.0436);.;
MVP		0.35
MPC		0.81
ClinPred		0.99	D
GERP RS		-1.1
Varity_R		0.23
gMVP		0.42

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: rs6767; hg19: chr2-3483205;