1-36139735-C-T

Variant names:

• chr1-36139735-C-T
• rs2231313
• NM_014408.5:c.225G>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_014408.5(TRAPPC3):​c.225G>A​(p.Ala75Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000586 in 1,614,090 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0027 (3 hom., cov: 31)
  • Exomes 𝑓: 0.00036 (1 hom.)
• Consequence: TRAPPC3 NM_014408.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.513
• Publications: 0 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP6: Variant 1-36139735-C-T is Benign according to our data. Variant chr1-36139735-C-T is described in ClinVar as Benign. ClinVar VariationId is 788504.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.513 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 3 gene

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.225G>A	p.Ala75Ala	synonymous	Exon 3 of 5	NP_055223.1	O43617-1
	TRAPPC3	NM_001270894.2		c.249G>A	p.Ala83Ala	synonymous	Exon 3 of 5	NP_001257823.1	A0A087WWM0
	TRAPPC3	NM_001270895.2		c.87G>A	p.Ala29Ala	synonymous	Exon 3 of 5	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.225G>A	p.Ala75Ala	synonymous	Exon 3 of 5	ENSP00000362261.3	O43617-1
	TRAPPC3	ENST00000923688.1		c.225G>A	p.Ala75Ala	synonymous	Exon 3 of 5	ENSP00000593747.1
	TRAPPC3	ENST00000616395.4	TSL:3	c.249G>A	p.Ala83Ala	synonymous	Exon 3 of 5	ENSP00000480332.1	A0A087WWM0

Frequencies

GnomAD3 genomes AF: 0.00272 AC: 414 AN: 152086 Hom.: 3 Cov.: 31

Gnomad AFR AF: 0.00939

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000459

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00192

GnomAD2 exomes AF: 0.000851 AC: 214 AN: 251428 AF XY: 0.000736

Gnomad AFR exome AF: 0.00929

Gnomad AMR exome AF: 0.000636

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000132

Gnomad OTH exome AF: 0.000815

GnomAD4 exome AF: 0.000363 AC: 530 AN: 1461886 Hom.: 1 Cov.: 31 AF XY: 0.000360 AC XY: 262 AN XY: 727242

African (AFR) AF: 0.00842 AC: 282 AN: 33480

American (AMR) AF: 0.000805 AC: 36 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000730 AC: 63 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

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

European-Non Finnish (NFE) AF: 0.0000863 AC: 96 AN: 1112006

Other (OTH) AF: 0.000861 AC: 52 AN: 60396

GnomAD4 genome AF: 0.00273 AC: 416 AN: 152204 Hom.: 3 Cov.: 31 AF XY: 0.00249 AC XY: 185 AN XY: 74418

African (AFR) AF: 0.00941 AC: 391 AN: 41532

American (AMR) AF: 0.000458 AC: 7 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

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

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68006

Other (OTH) AF: 0.00190 AC: 4 AN: 2110

Alfa AF: 0.00114 Hom.: 1

Bravo AF: 0.00286

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	8.9
DANN	Benign	0.71
PhyloP100		-0.51
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs2231313; hg19: chr1-36605336;