NM_016030.6:c.55C>T

Variant names:

• chr2-3387678-C-T
• rs752393610
• NM_016030.6:c.55C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016030.6(TRAPPC12):​c.55C>T​(p.Pro19Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000356 in 1,406,314 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P19T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000036 (0 hom.)
• Consequence: TRAPPC12 NM_016030.6 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: -1.10
• Publications: 1 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 Gene-Disease associations (from GenCC):

• early-onset progressive encephalopathy-hearing loss-pons hypoplasia-brain atrophy syndrome

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.039132923).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAPPC12	NM_016030.6	MANE Select	c.55C>T	p.Pro19Ser	missense	Exon 2 of 12	NP_057114.5
	TRAPPC12	NM_001321102.2		c.55C>T	p.Pro19Ser	missense	Exon 2 of 12	NP_001308031.1	Q8WVT3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAPPC12	ENST00000324266.10	TSL:1 MANE Select	c.55C>T	p.Pro19Ser	missense	Exon 2 of 12	ENSP00000324318.5	Q8WVT3
	TRAPPC12	ENST00000858088.1		c.55C>T	p.Pro19Ser	missense	Exon 2 of 13	ENSP00000528147.1
	TRAPPC12	ENST00000964175.1		c.55C>T	p.Pro19Ser	missense	Exon 2 of 13	ENSP00000634234.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000121 AC: 2 AN: 164850 AF XY: 0.00

Gnomad AFR exome AF: 0.000114

Gnomad AMR exome AF: 0.0000390

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000356 AC: 5 AN: 1406314 Hom.: 0 Cov.: 31 AF XY: 0.00000144 AC XY: 1 AN XY: 694566

African (AFR) AF: 0.0000944 AC: 3 AN: 31784

American (AMR) AF: 0.0000273 AC: 1 AN: 36626

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25226

East Asian (EAS) AF: 0.00 AC: 0 AN: 35936

South Asian (SAS) AF: 0.00 AC: 0 AN: 79846

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5708

European-Non Finnish (NFE) AF: 9.23e-7 AC: 1 AN: 1083420

Other (OTH) AF: 0.00 AC: 0 AN: 58348

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000340

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.0080
DANN	Benign	0.64
DEOGEN2	Benign	0.0050	T
Eigen	Benign	-2.2
Eigen_PC	Benign	-2.4
FATHMM_MKL	Benign	0.0054	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.32	N
PhyloP100		-1.1
PrimateAI	Benign	0.46	T
PROVEAN	Benign	0.22	N
REVEL	Benign	0.068
Sift	Benign	0.52	T
Sift4G	Benign	0.13	T
Polyphen		0.0020	B
Vest4		0.086
MutPred		0.14		Loss of catalytic residue at P18 (P = 0.0116)
MVP		0.076
MPC		0.25
ClinPred		0.013	T
GERP RS		-8.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.017
gMVP		0.079
Mutation Taster		=96/4	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: rs752393610; hg19: chr2-3391449;