NM_014408.5:c.424-20G>A

Variant names:

• chr1-36137342-C-T
• rs2231318
• NM_014408.5:c.424-20G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014408.5(TRAPPC3):​c.424-20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.756 in 1,599,800 control chromosomes in the GnomAD database, including 458,586 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.77 (45654 hom., cov: 31)
  • Exomes 𝑓: 0.75 (412932 hom.)
• Consequence: TRAPPC3 NM_014408.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.00700
• Publications: 11 publications found

Genes affected

TRAPPC3 (HGNC:19942): (trafficking protein particle complex subunit 3) This gene encodes a component of the trafficking protein particle complex, which tethers transport vesicles to the cis-Golgi membrane. The encoded protein participates in the regulation of transport from the endoplasmic reticulum to the Golgi apparatus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 2 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 1-36137342-C-T is Benign according to our data. Variant chr1-36137342-C-T is described in ClinVar as Benign. ClinVar VariationId is 1601300.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.827 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014408.5. 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
	TRAPPC3	NM_014408.5	MANE Select	c.424-20G>A		intron	N/A	NP_055223.1	O43617-1
	TRAPPC3	NM_001270894.2		c.448-20G>A		intron	N/A	NP_001257823.1	A0A087WWM0
	TRAPPC3	NM_001270895.2		c.286-20G>A		intron	N/A	NP_001257824.1	O43617-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAPPC3	ENST00000373166.8	TSL:1 MANE Select	c.424-20G>A		intron	N/A	ENSP00000362261.3	O43617-1
	TRAPPC3	ENST00000923688.1		c.449G>A	p.Arg150His	missense	Exon 5 of 5	ENSP00000593747.1
	TRAPPC3	ENST00000616395.4	TSL:3	c.448-20G>A		intron	N/A	ENSP00000480332.1	A0A087WWM0

Frequencies

GnomAD3 genomes AF: 0.772 AC: 117242 AN: 151952 Hom.: 45596 Cov.: 31

Gnomad AFR AF: 0.834

Gnomad AMI AF: 0.657

Gnomad AMR AF: 0.820

Gnomad ASJ AF: 0.657

Gnomad EAS AF: 0.702

Gnomad SAS AF: 0.662

Gnomad FIN AF: 0.665

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.760

Gnomad OTH AF: 0.755

GnomAD2 exomes AF: 0.745 AC: 185998 AN: 249674 AF XY: 0.738

Gnomad AFR exome AF: 0.839

Gnomad AMR exome AF: 0.844

Gnomad ASJ exome AF: 0.660

Gnomad EAS exome AF: 0.713

Gnomad FIN exome AF: 0.666

Gnomad NFE exome AF: 0.752

Gnomad OTH exome AF: 0.742

GnomAD4 exome AF: 0.754 AC: 1091423 AN: 1447730 Hom.: 412932 Cov.: 40 AF XY: 0.750 AC XY: 538161 AN XY: 717244

African (AFR) AF: 0.836 AC: 27842 AN: 33286

American (AMR) AF: 0.838 AC: 37304 AN: 44524

Ashkenazi Jewish (ASJ) AF: 0.659 AC: 17141 AN: 26016

East Asian (EAS) AF: 0.724 AC: 28400 AN: 39234

South Asian (SAS) AF: 0.663 AC: 56950 AN: 85866

European-Finnish (FIN) AF: 0.672 AC: 35800 AN: 53242

Middle Eastern (MID) AF: 0.705 AC: 3849 AN: 5460

European-Non Finnish (NFE) AF: 0.763 AC: 839689 AN: 1100454

Other (OTH) AF: 0.745 AC: 44448 AN: 59648

GnomAD4 genome AF: 0.772 AC: 117367 AN: 152070 Hom.: 45654 Cov.: 31 AF XY: 0.766 AC XY: 56908 AN XY: 74296

African (AFR) AF: 0.834 AC: 34603 AN: 41480

American (AMR) AF: 0.820 AC: 12542 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.657 AC: 2282 AN: 3472

East Asian (EAS) AF: 0.703 AC: 3635 AN: 5172

South Asian (SAS) AF: 0.663 AC: 3191 AN: 4814

European-Finnish (FIN) AF: 0.665 AC: 6995 AN: 10526

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.760 AC: 51710 AN: 68002

Other (OTH) AF: 0.756 AC: 1593 AN: 2106

Alfa AF: 0.767 Hom.: 73121

Bravo AF: 0.788

Asia WGS AF: 0.696 AC: 2423 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.8
DANN	Benign	0.58
PhyloP100		0.0070
BranchPoint Hunter		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs2231318; hg19: chr1-36602943; COSMIC: COSV107469850; COSMIC: COSV107469850;