rs6952

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• 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
• Publications: 26 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 -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 VariationId 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.

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.154T>G	p.Ser52Ala	missense	Exon 2 of 2	NP_001035927.1	Q8IUR0
	TRAPPC5	NM_001042461.3		c.154T>G	p.Ser52Ala	missense	Exon 2 of 2	NP_001035926.1	Q8IUR0
	TRAPPC5	NM_174894.3		c.154T>G	p.Ser52Ala	missense	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.154T>G	p.Ser52Ala	missense	Exon 2 of 2	ENSP00000470262.1	Q8IUR0
	TRAPPC5	ENST00000317378.5	TSL:1	c.154T>G	p.Ser52Ala	missense	Exon 2 of 2	ENSP00000316990.4	Q8IUR0
	ENSG00000269711	ENST00000597959.1	TSL:4	c.329T>G	p.Val110Gly	missense	Exon 3 of 3	ENSP00000469811.1	M0QYG6

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

GnomAD2 exomes AF: 0.289 AC: 54971 AN: 190532 AF XY: 0.293

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 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

African (AFR) AF: 0.544 AC: 17560 AN: 32292

American (AMR) AF: 0.158 AC: 6294 AN: 39740

Ashkenazi Jewish (ASJ) AF: 0.354 AC: 8916 AN: 25168

East Asian (EAS) AF: 0.235 AC: 8970 AN: 38146

South Asian (SAS) AF: 0.325 AC: 26927 AN: 82824

European-Finnish (FIN) AF: 0.312 AC: 15570 AN: 49932

Middle Eastern (MID) AF: 0.402 AC: 2154 AN: 5360

European-Non Finnish (NFE) AF: 0.305 AC: 334785 AN: 1096382

Other (OTH) AF: 0.324 AC: 19093 AN: 58952

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

African (AFR) AF: 0.540 AC: 22404 AN: 41506

American (AMR) AF: 0.245 AC: 3741 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.350 AC: 1213 AN: 3470

East Asian (EAS) AF: 0.267 AC: 1377 AN: 5164

South Asian (SAS) AF: 0.321 AC: 1549 AN: 4828

European-Finnish (FIN) AF: 0.315 AC: 3337 AN: 10592

Middle Eastern (MID) AF: 0.434 AC: 126 AN: 290

European-Non Finnish (NFE) AF: 0.311 AC: 21106 AN: 67934

Other (OTH) AF: 0.348 AC: 736 AN: 2116

Alfa AF: 0.323 Hom.: 4374

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

ClinVar submissions as Germline

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
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
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
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-0.28	N
PhyloP100		1.1
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.058
Sift	Benign	0.53	T
Sift4G	Benign	0.75	T
Polyphen		0.0	B
Vest4		0.028
MPC		0.99
ClinPred		0.0079	T
GERP RS		3.0
PromoterAI		-0.031	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.044
gMVP		0.56
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: rs6952; hg19: chr19-7747293; COSMIC: COSV58039587; COSMIC: COSV58039587;