2-3479434-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_016030.6(TRAPPC12):​c.2181C>T​(p.Phe727Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 1,613,654 control chromosomes in the GnomAD database, including 132,899 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (15499 hom., cov: 34)
  • Exomes 𝑓: 0.40 (117400 hom.)
• Consequence: TRAPPC12 NM_016030.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• 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: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 2-3479434-C-T is Benign according to our data. Variant chr2-3479434-C-T is described in ClinVar as Benign. ClinVar VariationId is 1342264.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.602 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAPPC12	NM_016030.6	c.2181C>T	p.Phe727Phe	synonymous_variant	Exon 12 of 12	ENST00000324266.10	NP_057114.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAPPC12	ENST00000324266.10	c.2181C>T	p.Phe727Phe	synonymous_variant	Exon 12 of 12	1	NM_016030.6	ENSP00000324318.5

Frequencies

GnomAD3 genomes AF: 0.443 AC: 67339 AN: 152054 Hom.: 15493 Cov.: 34

Gnomad AFR AF: 0.562

Gnomad AMI AF: 0.709

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.479

Gnomad EAS AF: 0.486

Gnomad SAS AF: 0.499

Gnomad FIN AF: 0.426

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.437

GnomAD2 exomes AF: 0.416 AC: 104208 AN: 250562 AF XY: 0.419

Gnomad AFR exome AF: 0.564

Gnomad AMR exome AF: 0.323

Gnomad ASJ exome AF: 0.482

Gnomad EAS exome AF: 0.485

Gnomad FIN exome AF: 0.421

Gnomad NFE exome AF: 0.382

Gnomad OTH exome AF: 0.421

GnomAD4 exome AF: 0.397 AC: 580341 AN: 1461482 Hom.: 117400 Cov.: 52 AF XY: 0.401 AC XY: 291489 AN XY: 727056

African (AFR) AF: 0.566 AC: 18959 AN: 33478

American (AMR) AF: 0.328 AC: 14682 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 12600 AN: 26136

East Asian (EAS) AF: 0.504 AC: 19991 AN: 39694

South Asian (SAS) AF: 0.501 AC: 43179 AN: 86252

European-Finnish (FIN) AF: 0.413 AC: 21936 AN: 53168

Middle Eastern (MID) AF: 0.496 AC: 2863 AN: 5768

European-Non Finnish (NFE) AF: 0.378 AC: 420789 AN: 1111884

Other (OTH) AF: 0.420 AC: 25342 AN: 60384

GnomAD4 genome AF: 0.443 AC: 67379 AN: 152172 Hom.: 15499 Cov.: 34 AF XY: 0.441 AC XY: 32820 AN XY: 74390

African (AFR) AF: 0.562 AC: 23334 AN: 41504

American (AMR) AF: 0.361 AC: 5530 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.479 AC: 1660 AN: 3468

East Asian (EAS) AF: 0.485 AC: 2510 AN: 5174

South Asian (SAS) AF: 0.499 AC: 2400 AN: 4814

European-Finnish (FIN) AF: 0.426 AC: 4508 AN: 10582

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.378 AC: 25736 AN: 68008

Other (OTH) AF: 0.434 AC: 916 AN: 2110

Alfa AF: 0.402 Hom.: 24905

Bravo AF: 0.446

Asia WGS AF: 0.503 AC: 1751 AN: 3478

EpiCase AF: 0.394

EpiControl AF: 0.394

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Early-onset progressive encephalopathy-hearing loss-pons hypoplasia-brain atrophy syndrome Benign:1

Sep 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

TRAPPC12-related disorder Benign:1

Oct 16, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	2.1
DANN	Benign	0.85
PhyloP100		0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Mutation Taster		=97/3	polymorphism (auto)

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; COSMIC: COSV60852347; COSMIC: COSV60852347;