19-7682548-G-C

Variant names:

• chr19-7682548-G-C
• rs539921515
• NM_001042462.2:c.295G>C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001042462.2(TRAPPC5):​c.295G>C​(p.Gly99Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000656 in 152,330 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: TRAPPC5 NM_001042462.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.35

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 Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.838

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAPPC5	NM_001042462.2	c.295G>C	p.Gly99Arg	missense_variant	Exon 2 of 2	ENST00000596148.3	NP_001035927.1
TRAPPC5	NM_001042461.3	c.295G>C	p.Gly99Arg	missense_variant	Exon 2 of 2		NP_001035926.1
TRAPPC5	NM_174894.3	c.295G>C	p.Gly99Arg	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.295G>C	p.Gly99Arg	missense_variant	Exon 2 of 2	1	NM_001042462.2	ENSP00000470262.1
ENSG00000269711	ENST00000597959.1	c.*59G>C		3_prime_UTR_variant	Exon 3 of 3	4		ENSP00000469811.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152212 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00000406 AC: 1 AN: 246210 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 134146

Gnomad AFR exome AF: 0.0000651

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome AF: 0.00000656 AC: 1 AN: 152330 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74500

Gnomad4 AFR AF: 0.0000240

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ExAC AF: 0.00000825 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.85
BayesDel_addAF	Uncertain	0.042	T
BayesDel_noAF	Uncertain	0.0
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	T;T;T;.
Eigen	Pathogenic	0.77
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	1.0	.;.;D;D
M_CAP	Uncertain	0.24	D
MetaRNN	Pathogenic	0.84	D;D;D;D
MetaSVM	Uncertain	-0.13	T
MutationAssessor	Pathogenic	3.1	M;M;M;.
PrimateAI	Pathogenic	0.92	D
PROVEAN	Pathogenic	-7.7	.;D;D;.
REVEL	Uncertain	0.55
Sift	Uncertain	0.0010	.;D;D;.
Sift4G	Uncertain	0.0040	D;D;D;D
Polyphen		1.0	D;D;D;.
Vest4		0.73
MutPred		0.73		Gain of MoRF binding (P = 0.0087);Gain of MoRF binding (P = 0.0087);Gain of MoRF binding (P = 0.0087);.;
MVP		0.27
MPC		2.6
ClinPred		1.0	D
GERP RS		3.0
Varity_R		0.97
gMVP		0.93

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: rs539921515; hg19: chr19-7747434;