Genetic Variant NM_016030.6:c.38C>G (chr2-3387661-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_016030.6(TRAPPC12):c.38C>G(p.Pro13Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000716 in 1,396,978 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P13L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

TRAPPC12
NM_016030.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0540

Publications

0 publications found

Variant links:

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

TRAPPC12 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.06291169).

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.38C>G	p.Pro13Arg	missense	Exon 2 of 12	NP_057114.5
	TRAPPC12	NM_001321102.2		c.38C>G	p.Pro13Arg	missense	Exon 2 of 12	NP_001308031.1	Q8WVT3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRAPPC12	ENST00000324266.10	TSL:1 MANE Select	c.38C>G	p.Pro13Arg	missense	Exon 2 of 12	ENSP00000324318.5	Q8WVT3
TRAPPC12	ENST00000858088.1		c.38C>G	p.Pro13Arg	missense	Exon 2 of 13	ENSP00000528147.1
TRAPPC12	ENST00000964175.1		c.38C>G	p.Pro13Arg	missense	Exon 2 of 13	ENSP00000634234.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

152778

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

7.16e-7

AC:

AN:

1396978

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

688636

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31528

American (AMR)

AF:

0.00

AC:

AN:

35590

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25122

East Asian (EAS)

AF:

0.00

AC:

AN:

35606

South Asian (SAS)

AF:

0.00

AC:

AN:

79184

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48792

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5688

European-Non Finnish (NFE)

AF:

9.28e-7

AC:

AN:

1077556

Other (OTH)

AF:

0.00

AC:

AN:

57912

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

5.5

(source)

DANN

Benign

0.53

DEOGEN2

Benign

0.0051

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.042

LIST_S2

Benign

0.39

M_CAP

Benign

0.035

MetaRNN

Benign

0.063

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.5

PhyloP100

0.054

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.48

REVEL

Benign

0.097

Sift

Benign

0.046

Sift4G

Uncertain

0.028

Polyphen

0.090

Vest4

0.089

MutPred

0.18

Loss of glycosylation at P13 (P = 0.0309)

MVP

0.17

MPC

0.26

ClinPred

0.15

GERP RS

-3.0

Varity_R

0.036

gMVP

0.071

Mutation Taster

=96/4

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over