rs6952

Variant names:

• chr19-7682407-T-G
• rs6952
• NM_001042462.2:c.154T>G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001042462.2(TRAPPC5):​c.154T>G​(p.Ser52Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 1,580,882 control chromosomes in the GnomAD database, including 80,967 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.37 (11252 hom., cov: 33)
  • Exomes 𝑓: 0.31 (69715 hom.)
• Consequence: TRAPPC5 NM_001042462.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.13

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

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.4992228E-4).
• BP6: Variant 19-7682407-T-G is Benign according to our data. Variant chr19-7682407-T-G is described in ClinVar as [Benign]. Clinvar id is 1327245.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAPPC5	NM_001042462.2	c.154T>G	p.Ser52Ala	missense_variant	Exon 2 of 2	ENST00000596148.3	NP_001035927.1
TRAPPC5	NM_001042461.3	c.154T>G	p.Ser52Ala	missense_variant	Exon 2 of 2		NP_001035926.1
TRAPPC5	NM_174894.3	c.154T>G	p.Ser52Ala	missense_variant	Exon 2 of 2		NP_777554.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAPPC5	ENST00000596148.3	c.154T>G	p.Ser52Ala	missense_variant	Exon 2 of 2	1	NM_001042462.2	ENSP00000470262.1
ENSG00000269711	ENST00000597959.1	c.329T>G	p.Val110Gly	missense_variant	Exon 3 of 3	4		ENSP00000469811.1

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55848 AN: 151978 Hom.: 11238 Cov.: 33

Gnomad AFR AF: 0.540

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.267

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.315

Gnomad MID AF: 0.429

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.352

GnomAD3 exomes AF: 0.289 AC: 54971 AN: 190532 Hom.: 8756 AF XY: 0.293 AC XY: 30778 AN XY: 104932

Gnomad AFR exome AF: 0.527

Gnomad AMR exome AF: 0.146

Gnomad ASJ exome AF: 0.354

Gnomad EAS exome AF: 0.257

Gnomad SAS exome AF: 0.316

Gnomad FIN exome AF: 0.307

Gnomad NFE exome AF: 0.296

Gnomad OTH exome AF: 0.288

GnomAD4 exome AF: 0.308 AC: 440269 AN: 1428796 Hom.: 69715 Cov.: 36 AF XY: 0.309 AC XY: 218790 AN XY: 708360

Gnomad4 AFR exome AF: 0.544

Gnomad4 AMR exome AF: 0.158

Gnomad4 ASJ exome AF: 0.354

Gnomad4 EAS exome AF: 0.235

Gnomad4 SAS exome AF: 0.325

Gnomad4 FIN exome AF: 0.312

Gnomad4 NFE exome AF: 0.305

Gnomad4 OTH exome AF: 0.324

GnomAD4 genome AF: 0.367 AC: 55883 AN: 152086 Hom.: 11252 Cov.: 33 AF XY: 0.363 AC XY: 27021 AN XY: 74346

Gnomad4 AFR AF: 0.540

Gnomad4 AMR AF: 0.245

Gnomad4 ASJ AF: 0.350

Gnomad4 EAS AF: 0.267

Gnomad4 SAS AF: 0.321

Gnomad4 FIN AF: 0.315

Gnomad4 NFE AF: 0.311

Gnomad4 OTH AF: 0.348

Alfa AF: 0.329 Hom.: 2688

Bravo AF: 0.367

TwinsUK AF: 0.321 AC: 1191

ALSPAC AF: 0.310 AC: 1196

ESP6500AA AF: 0.454 AC: 1566

ESP6500EA AF: 0.270 AC: 1982

ExAC AF: 0.251 AC: 27773

Asia WGS AF: 0.279 AC: 968 AN: 3466

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 03, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	19
DANN	Benign	0.87
DEOGEN2	Benign	0.0053	T;T;T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.081	N
LIST_S2	Benign	0.26	.;.;T
MetaRNN	Benign	0.00025	T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-0.28	N;N;N
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.1	.;N;N
REVEL	Benign	0.058
Sift	Benign	0.53	.;T;T
Sift4G	Benign	0.75	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.028
MPC		0.99
ClinPred		0.0079	T
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.044
gMVP		0.56

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

Publications

LitVar

Other links and lift over

dbSNP: rs6952; hg19: chr19-7747293; COSMIC: COSV58039587; COSMIC: COSV58039587;