17-7931012-G-T

Variant names:

• chr17-7931012-G-T
• rs780139319
• NM_021210.5:c.308C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021210.5(TRAPPC1):​c.308C>A​(p.Ala103Glu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,496 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. 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. A103V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: TRAPPC1 NM_021210.5 missense, splice_region
• Scores: Splicing: ADA: 0.001663
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.61
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15845251).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021210.5. 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
	TRAPPC1	NM_021210.5	MANE Select	c.308C>A	p.Ala103Glu	missense splice_region	Exon 3 of 4	NP_067033.1	Q9Y5R8
	TRAPPC1	NM_001166621.1		c.308C>A	p.Ala103Glu	missense splice_region	Exon 4 of 5	NP_001160093.1	Q9Y5R8
	TRAPPC1	NR_030684.2		n.354C>A		splice_region non_coding_transcript_exon	Exon 2 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAPPC1	ENST00000303731.9	TSL:1 MANE Select	c.308C>A	p.Ala103Glu	missense splice_region	Exon 3 of 4	ENSP00000302783.4	Q9Y5R8
	TRAPPC1	ENST00000540486.5	TSL:2	c.308C>A	p.Ala103Glu	missense splice_region	Exon 4 of 5	ENSP00000441130.1	Q9Y5R8
	TRAPPC1	ENST00000968005.1		c.305C>A	p.Ala102Glu	missense splice_region	Exon 3 of 4	ENSP00000638064.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461496 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727048

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26102

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5656

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111876

Other (OTH) AF: 0.0000166 AC: 1 AN: 60360

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	22
DANN	Benign	0.87
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.90	N
PhyloP100		2.6
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	1.2	N
REVEL	Benign	0.13
Sift	Benign	0.89	T
Sift4G	Benign	0.75	T
Polyphen		0.0020	B
Vest4		0.42
MutPred		0.55		Gain of helix (P = 0.132)
MVP		0.16
MPC		0.91
ClinPred		0.71	D
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.52
Mutation Taster		=82/18	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0017
dbscSNV1_RF	Benign	0.094
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: rs780139319; hg19: chr17-7834330;