NM_016030.6:c.2181C>A

Variant names:

• chr2-3479434-C-A
• rs6767
• NM_016030.6:c.2181C>A

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 37 publications found

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:41046): (TRAPPC12 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016030.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAPPC12	NM_016030.6	MANE Select	c.2181C>A	p.Phe727Leu	missense	Exon 12 of 12	NP_057114.5
	TRAPPC12	NM_001321102.2		c.2181C>A	p.Phe727Leu	missense	Exon 12 of 12	NP_001308031.1
	TRAPPC12-AS1	NR_046720.1		n.3560G>T		non_coding_transcript_exon	Exon 2 of 2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAPPC12	ENST00000324266.10	TSL:1 MANE Select	c.2181C>A	p.Phe727Leu	missense	Exon 12 of 12	ENSP00000324318.5
	TRAPPC12	ENST00000382110.6	TSL:2	c.2181C>A	p.Phe727Leu	missense	Exon 12 of 12	ENSP00000371544.2
	TRAPPC12	ENST00000415624.5	TSL:5	c.678C>A	p.Phe226Leu	missense	Exon 7 of 7	ENSP00000396592.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 52

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.50
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.057	D
MetaRNN	Uncertain	0.64	D
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.60
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-2.7	D
REVEL	Uncertain	0.32
Sift	Benign	0.18	T
Sift4G	Benign	0.35	T
Polyphen		0.93	P
Vest4		0.77
MutPred		0.36		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
Mutation Taster		=62/38	polymorphism

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

Other links and lift over

dbSNP: rs6767; hg19: chr2-3483205;