5-65647101-A-T

Variant names:

• chr5-65647101-A-T
• rs757913989
• NM_024941.4:c.347A>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.-125A>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000128 in 1,561,148 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: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: TRAPPC13 NM_001365342.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.43
• 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=0.16464093).

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.347A>T	p.Asn116Ile	missense	Exon 5 of 13	NP_079217.2	A5PLN9-1
	TRAPPC13	NM_001365342.1		c.-125A>T		5_prime_UTR_premature_start_codon_gain	Exon 4 of 11	NP_001352271.1
	TRAPPC13	NM_001365343.1		c.-125A>T		5_prime_UTR_premature_start_codon_gain	Exon 4 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.347A>T	p.Asn116Ile	missense	Exon 5 of 13	ENSP00000382367.3	A5PLN9-1
	TRAPPC13	ENST00000438419.6	TSL:1	c.347A>T	p.Asn116Ile	missense	Exon 5 of 13	ENSP00000409231.2	A5PLN9-5
	TRAPPC13	ENST00000505553.5	TSL:1	c.347A>T	p.Asn116Ile	missense	Exon 5 of 12	ENSP00000423405.1	A5PLN9-4

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151932 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 7.10e-7 AC: 1 AN: 1409216 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 695870

African (AFR) AF: 0.00 AC: 0 AN: 32390

American (AMR) AF: 0.00 AC: 0 AN: 36492

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25324

East Asian (EAS) AF: 0.00 AC: 0 AN: 37596

South Asian (SAS) AF: 0.00 AC: 0 AN: 80036

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50104

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5710

European-Non Finnish (NFE) AF: 9.23e-7 AC: 1 AN: 1083120

Other (OTH) AF: 0.00 AC: 0 AN: 58444

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151932 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74202

African (AFR) AF: 0.00 AC: 0 AN: 41364

American (AMR) AF: 0.00 AC: 0 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10552

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67984

Other (OTH) AF: 0.00 AC: 0 AN: 2088

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	Benign	0.14
BayesDel_addAF	Benign	-0.025	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.049
FATHMM_MKL	Benign	0.68	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.0096	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.7	L
PhyloP100		1.4
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.12
Sift	Uncertain	0.029	D
Sift4G	Benign	0.15	T
Polyphen		0.015	B
Vest4		0.42
MutPred		0.42		Loss of disorder (P = 0.0276)
MVP		0.068
MPC		0.49
ClinPred		0.79	D
GERP RS		3.2
Varity_R		0.25
gMVP		0.26
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: rs757913989; hg19: chr5-64942928;