19-7682559-G-A

Variant names:

• chr19-7682559-G-A
• rs1053363
• NM_001042462.2:c.306G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001042462.2(TRAPPC5):​c.306G>A​(p.Ala102Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 1,612,408 control chromosomes in the GnomAD database, including 27,444 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4928 hom., cov: 33)
  • Exomes 𝑓: 0.17 (22516 hom.)
• Consequence: TRAPPC5 NM_001042462.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -5.49
• Publications: 18 publications found

Genes affected

TRAPPC5 (HGNC:23067): (trafficking protein particle complex subunit 5) Predicted to be involved in endoplasmic reticulum to Golgi vesicle-mediated transport. Part of TRAPP complex. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000269711 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 19-7682559-G-A is Benign according to our data. Variant chr19-7682559-G-A is described in ClinVar as Benign. ClinVar VariationId is 1327246.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-5.49 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042462.2. 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
	TRAPPC5	NM_001042462.2	MANE Select	c.306G>A	p.Ala102Ala	synonymous	Exon 2 of 2	NP_001035927.1	Q8IUR0
	TRAPPC5	NM_001042461.3		c.306G>A	p.Ala102Ala	synonymous	Exon 2 of 2	NP_001035926.1	Q8IUR0
	TRAPPC5	NM_174894.3		c.306G>A	p.Ala102Ala	synonymous	Exon 2 of 2	NP_777554.1	Q8IUR0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAPPC5	ENST00000596148.3	TSL:1 MANE Select	c.306G>A	p.Ala102Ala	synonymous	Exon 2 of 2	ENSP00000470262.1	Q8IUR0
	TRAPPC5	ENST00000317378.5	TSL:1	c.306G>A	p.Ala102Ala	synonymous	Exon 2 of 2	ENSP00000316990.4	Q8IUR0
	ENSG00000269711	ENST00000597959.1	TSL:4	c.*70G>A		3_prime_UTR	Exon 3 of 3	ENSP00000469811.1	M0QYG6

Frequencies

GnomAD3 genomes AF: 0.230 AC: 35040 AN: 152076 Hom.: 4922 Cov.: 33

Gnomad AFR AF: 0.398

Gnomad AMI AF: 0.0615

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.228

GnomAD2 exomes AF: 0.183 AC: 45056 AN: 246132 AF XY: 0.186

Gnomad AFR exome AF: 0.408

Gnomad AMR exome AF: 0.108

Gnomad ASJ exome AF: 0.187

Gnomad EAS exome AF: 0.148

Gnomad FIN exome AF: 0.166

Gnomad NFE exome AF: 0.166

Gnomad OTH exome AF: 0.186

GnomAD4 exome AF: 0.169 AC: 246062 AN: 1460214 Hom.: 22516 Cov.: 33 AF XY: 0.171 AC XY: 124078 AN XY: 726522

African (AFR) AF: 0.411 AC: 13750 AN: 33476

American (AMR) AF: 0.114 AC: 5087 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 4869 AN: 26122

East Asian (EAS) AF: 0.103 AC: 4071 AN: 39694

South Asian (SAS) AF: 0.243 AC: 20994 AN: 86250

European-Finnish (FIN) AF: 0.166 AC: 8588 AN: 51882

Middle Eastern (MID) AF: 0.317 AC: 1831 AN: 5768

European-Non Finnish (NFE) AF: 0.158 AC: 175338 AN: 1111934

Other (OTH) AF: 0.191 AC: 11534 AN: 60374

GnomAD4 genome AF: 0.231 AC: 35081 AN: 152194 Hom.: 4928 Cov.: 33 AF XY: 0.230 AC XY: 17104 AN XY: 74406

African (AFR) AF: 0.398 AC: 16528 AN: 41530

American (AMR) AF: 0.175 AC: 2683 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 631 AN: 3472

East Asian (EAS) AF: 0.130 AC: 674 AN: 5174

South Asian (SAS) AF: 0.242 AC: 1168 AN: 4824

European-Finnish (FIN) AF: 0.171 AC: 1809 AN: 10598

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.161 AC: 10952 AN: 67980

Other (OTH) AF: 0.226 AC: 477 AN: 2110

Alfa AF: 0.189 Hom.: 2324

Bravo AF: 0.235

Asia WGS AF: 0.201 AC: 697 AN: 3478

EpiCase AF: 0.167

EpiControl AF: 0.167

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	-0.65
CADD	Benign	5.5
DANN	Benign	0.95
PhyloP100		-5.5
PromoterAI		-0.0072	Neutral
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: rs1053363; hg19: chr19-7747445; COSMIC: COSV58039381; COSMIC: COSV58039381;