rs10193454

Variant names:

• chr2-3453326-G-A
• rs10193454
• NM_016030.6:c.1531-4295G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-3453326-G-A
• chr2-3453326-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016030.6(TRAPPC12):​c.1531-4295G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 152,114 control chromosomes in the GnomAD database, including 3,484 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.19 (3484 hom., cov: 33)
• Consequence: TRAPPC12 NM_016030.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0850
• Publications: 3 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: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

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.1531-4295G>A		intron	N/A	NP_057114.5
	TRAPPC12	NM_001321102.2		c.1531-4295G>A		intron	N/A	NP_001308031.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAPPC12	ENST00000324266.10	TSL:1 MANE Select	c.1531-4295G>A		intron	N/A	ENSP00000324318.5
	TRAPPC12	ENST00000382110.6	TSL:2	c.1531-4295G>A		intron	N/A	ENSP00000371544.2
	TRAPPC12	ENST00000415624.5	TSL:5	c.25-4295G>A		intron	N/A	ENSP00000396592.1

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29244 AN: 151996 Hom.: 3469 Cov.: 33

Gnomad AFR AF: 0.332

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.209

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.193 AC: 29296 AN: 152114 Hom.: 3484 Cov.: 33 AF XY: 0.191 AC XY: 14232 AN XY: 74348

African (AFR) AF: 0.332 AC: 13777 AN: 41482

American (AMR) AF: 0.147 AC: 2256 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 907 AN: 3470

East Asian (EAS) AF: 0.182 AC: 944 AN: 5176

South Asian (SAS) AF: 0.123 AC: 593 AN: 4822

European-Finnish (FIN) AF: 0.123 AC: 1300 AN: 10590

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.130 AC: 8819 AN: 67960

Other (OTH) AF: 0.206 AC: 436 AN: 2112

Alfa AF: 0.146 Hom.: 366

Bravo AF: 0.202

Asia WGS AF: 0.158 AC: 552 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.7
DANN	Benign	0.53
PhyloP100		0.085
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Mutation Taster		=100/0	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: rs10193454; hg19: chr2-3457097;