chr5-65636006-A-T

Variant names:

• chr5-65636006-A-T
• rs1755731776
• NM_024941.4:c.178A>T

Variant summary

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

The NM_001365342.1(TRAPPC13):​c.-209A>T variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.00000069 in 1,448,790 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.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TRAPPC13 NM_001365342.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.87
• Publications: 0 publications found

Genes affected

TRAPPC13 (HGNC:25828): (trafficking protein particle complex subunit 13) Predicted to be located in cytosol. Predicted to be part of TRAPPIII protein complex. [provided by Alliance of Genome Resources, Apr 2022]

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=0.23298565).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365342.1. 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
	TRAPPC13	NM_024941.4	MANE Select	c.178A>T	p.Met60Leu	missense	Exon 3 of 13	NP_079217.2	A5PLN9-1
	TRAPPC13	NM_001365342.1		c.-209A>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 11	NP_001352271.1
	TRAPPC13	NM_001365343.1		c.-209A>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 11	NP_001352272.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAPPC13	ENST00000399438.8	TSL:2 MANE Select	c.178A>T	p.Met60Leu	missense	Exon 3 of 13	ENSP00000382367.3	A5PLN9-1
	TRAPPC13	ENST00000438419.6	TSL:1	c.178A>T	p.Met60Leu	missense	Exon 3 of 13	ENSP00000409231.2	A5PLN9-5
	TRAPPC13	ENST00000505553.5	TSL:1	c.178A>T	p.Met60Leu	missense	Exon 3 of 12	ENSP00000423405.1	A5PLN9-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1448790 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 719004

African (AFR) AF: 0.00 AC: 0 AN: 33376

American (AMR) AF: 0.00 AC: 0 AN: 43030

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25796

East Asian (EAS) AF: 0.00 AC: 0 AN: 39506

South Asian (SAS) AF: 0.00 AC: 0 AN: 83428

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52780

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 9.05e-7 AC: 1 AN: 1105166

Other (OTH) AF: 0.00 AC: 0 AN: 59962

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Uncertain	0.030	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.0096	T
Eigen	Benign	0.062
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.12	N
PhyloP100		6.9
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-0.53	N
REVEL	Benign	0.24
Sift	Benign	0.084	T
Sift4G	Benign	0.18	T
Polyphen		0.0	B
Vest4		0.43
MutPred		0.36		Gain of helix (P = 0.132)
MVP		0.18
MPC		0.36
ClinPred		0.61	D
GERP RS		5.7
Varity_R		0.25
gMVP		0.36
Mutation Taster		=77/23	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: rs1755731776; hg19: chr5-64931833;