19-7682411-G-T

Variant names:

• chr19-7682411-G-T
• rs771166688
• NM_001042462.2:c.158G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001042462.2(TRAPPC5):​c.158G>T​(p.Arg53Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000139 in 1,435,508 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R53H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TRAPPC5 NM_001042462.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.32
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37571448).

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.158G>T	p.Arg53Leu	missense	Exon 2 of 2	NP_001035927.1	Q8IUR0
	TRAPPC5	NM_001042461.3		c.158G>T	p.Arg53Leu	missense	Exon 2 of 2	NP_001035926.1	Q8IUR0
	TRAPPC5	NM_174894.3		c.158G>T	p.Arg53Leu	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.158G>T	p.Arg53Leu	missense	Exon 2 of 2	ENSP00000470262.1	Q8IUR0
	TRAPPC5	ENST00000317378.5	TSL:1	c.158G>T	p.Arg53Leu	missense	Exon 2 of 2	ENSP00000316990.4	Q8IUR0
	ENSG00000269711	ENST00000597959.1	TSL:4	c.333G>T	p.Ala111Ala	synonymous	Exon 3 of 3	ENSP00000469811.1	M0QYG6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000151 AC: 3 AN: 198262 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000101

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1435508 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 712240

African (AFR) AF: 0.00 AC: 0 AN: 32540

American (AMR) AF: 0.0000492 AC: 2 AN: 40662

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25288

East Asian (EAS) AF: 0.00 AC: 0 AN: 38552

South Asian (SAS) AF: 0.00 AC: 0 AN: 83544

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50332

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5370

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1099992

Other (OTH) AF: 0.00 AC: 0 AN: 59228

GnomAD4 genome Cov.: 33

Alfa AF: 0.000109 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000871 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Benign	-0.020	T
BayesDel_noAF	Benign	-0.27
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.082	T
Eigen	Benign	-0.0097
Eigen_PC	Benign	-0.045
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.94	D
M_CAP	Uncertain	0.22	D
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		4.3
PrimateAI	Pathogenic	0.86	D
PROVEAN	Pathogenic	-4.4	D
REVEL	Benign	0.23
Sift	Uncertain	0.017	D
Sift4G	Benign	0.082	T
Polyphen		0.83	P
Vest4		0.42
MutPred		0.69		Loss of MoRF binding (P = 0.0065)
MVP		0.082
MPC		1.7
ClinPred		0.88	D
GERP RS		1.9
PromoterAI		0.019	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.37
gMVP		0.98
Mutation Taster		=68/32	polymorphism

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: rs771166688; hg19: chr19-7747297;