rs576484394

Variant names:

• chr17-7930707-G-C
• rs576484394
• NM_021210.5:c.337C>G

Your query was ambiguous. Multiple possible variants found:

• chr17-7930707-G-C
• chr17-7930707-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_021210.5(TRAPPC1):​c.337C>G​(p.Pro113Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,856 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: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TRAPPC1 NM_021210.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.92

Genes affected

TRAPPC1 (HGNC:19894): (trafficking protein particle complex subunit 1) This gene product plays a role in vesicular transport of proteins to the Golgi apparatus from the endoplasmic reticulum. The encoded protein is a component of the multisubunit transport protein particle (TRAPP) complex. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Oct 2009]

ENSG00000262730 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.917

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAPPC1	NM_021210.5	c.337C>G	p.Pro113Ala	missense_variant	Exon 4 of 4	ENST00000303731.9	NP_067033.1
TRAPPC1	NM_001166621.1	c.337C>G	p.Pro113Ala	missense_variant	Exon 5 of 5		NP_001160093.1
TRAPPC1	NR_030684.2	n.383C>G		non_coding_transcript_exon_variant	Exon 3 of 3
TRAPPC1	NR_030697.1	n.326C>G		non_coding_transcript_exon_variant	Exon 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAPPC1	ENST00000303731.9	c.337C>G	p.Pro113Ala	missense_variant	Exon 4 of 4	1	NM_021210.5	ENSP00000302783.4
ENSG00000262730	ENST00000573621.1	n.-87C>G		upstream_gene_variant		5		ENSP00000461816.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461856 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727226

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.23
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.33	T;T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.96	D;.
M_CAP	Uncertain	0.23	D
MetaRNN	Pathogenic	0.92	D;D
MetaSVM	Uncertain	0.67	D
MutationAssessor	Uncertain	2.7	M;M
PrimateAI	Uncertain	0.71	T
PROVEAN	Pathogenic	-6.2	D;D
REVEL	Pathogenic	0.80
Sift	Benign	0.088	T;T
Sift4G	Benign	0.071	T;T
Polyphen		0.98	D;D
Vest4		0.63
MutPred		0.87		Gain of ubiquitination at K111 (P = 0.0822);Gain of ubiquitination at K111 (P = 0.0822);
MVP		0.98
MPC		1.5
ClinPred		0.97	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.28
gMVP		0.70

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: rs576484394; hg19: chr17-7834025;