rs117747228

Variant names:

• chr2-3387768-G-A
• rs117747228
• NM_016030.6:c.145G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-3387768-G-A
• chr2-3387768-G-C
• chr2-3387768-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_016030.6(TRAPPC12):​c.145G>A​(p.Glu49Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000732 in 1,612,926 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00089 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00072 (2 hom.)
• Consequence: TRAPPC12 NM_016030.6 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 7.27
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0049600303).
• BP6: Variant 2-3387768-G-A is Benign according to our data. Variant chr2-3387768-G-A is described in ClinVar as Benign. ClinVar VariationId is 1530005.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000893 (136/152356) while in subpopulation EAS AF = 0.0162 (84/5188). AF 95% confidence interval is 0.0134. There are 1 homozygotes in GnomAd4. There are 78 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

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.145G>A	p.Glu49Lys	missense	Exon 2 of 12	NP_057114.5
	TRAPPC12	NM_001321102.2		c.145G>A	p.Glu49Lys	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.145G>A	p.Glu49Lys	missense	Exon 2 of 12	ENSP00000324318.5	Q8WVT3
	TRAPPC12	ENST00000858088.1		c.145G>A	p.Glu49Lys	missense	Exon 2 of 13	ENSP00000528147.1
	TRAPPC12	ENST00000964175.1		c.145G>A	p.Glu49Lys	missense	Exon 2 of 13	ENSP00000634234.1

Frequencies

GnomAD3 genomes AF: 0.000900 AC: 137 AN: 152238 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.0162

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00185 AC: 459 AN: 248264 AF XY: 0.00155

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00582

Gnomad ASJ exome AF: 0.0000999

Gnomad EAS exome AF: 0.0126

Gnomad FIN exome AF: 0.0000465

Gnomad NFE exome AF: 0.0000625

Gnomad OTH exome AF: 0.00249

GnomAD4 exome AF: 0.000715 AC: 1045 AN: 1460570 Hom.: 2 Cov.: 31 AF XY: 0.000644 AC XY: 468 AN XY: 726506

African (AFR) AF: 0.0000299 AC: 1 AN: 33430

American (AMR) AF: 0.00538 AC: 240 AN: 44650

Ashkenazi Jewish (ASJ) AF: 0.000115 AC: 3 AN: 26102

East Asian (EAS) AF: 0.0164 AC: 650 AN: 39600

South Asian (SAS) AF: 0.000407 AC: 35 AN: 85996

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53326

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.0000360 AC: 40 AN: 1111388

Other (OTH) AF: 0.00123 AC: 74 AN: 60310

GnomAD4 genome AF: 0.000893 AC: 136 AN: 152356 Hom.: 1 Cov.: 33 AF XY: 0.00105 AC XY: 78 AN XY: 74510

African (AFR) AF: 0.000144 AC: 6 AN: 41582

American (AMR) AF: 0.00216 AC: 33 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.0162 AC: 84 AN: 5188

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4828

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68030

Other (OTH) AF: 0.00142 AC: 3 AN: 2116

Alfa AF: 0.000650 Hom.: 1

Bravo AF: 0.00104

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00174 AC: 211

Asia WGS AF: 0.00664 AC: 23 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.0000594

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	TRAPPC12-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.030	T
Eigen	Uncertain	0.22
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.88	D
MetaRNN	Benign	0.0050	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		7.3
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.093
Sift	Benign	0.042	D
Sift4G	Benign	0.24	T
Polyphen		0.98	D
Vest4		0.22
MVP		0.62
MPC		0.48
ClinPred		0.060	T
GERP RS		5.0
Varity_R		0.16
gMVP		0.20
Mutation Taster		=98/2	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: rs117747228; hg19: chr2-3391539; COSMIC: COSV109425329; COSMIC: COSV109425329;