5-65637736-G-T

Variant names:

• chr5-65637736-G-T
• NM_024941.4:c.256G>T

Variant summary

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

The NM_024941.4(TRAPPC13):​c.256G>T​(p.Val86Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000704 in 1,420,486 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: 30)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: TRAPPC13 NM_024941.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.24

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

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, 0.933

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAPPC13	NM_024941.4	c.256G>T	p.Val86Phe	missense_variant	Exon 4 of 13	ENST00000399438.8	NP_079217.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAPPC13	ENST00000399438.8	c.256G>T	p.Val86Phe	missense_variant	Exon 4 of 13	2	NM_024941.4	ENSP00000382367.3

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 7.04e-7 AC: 1 AN: 1420486 Hom.: 0 Cov.: 26 AF XY: 0.00000141 AC XY: 1 AN XY: 707580

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000257

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.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.46	D
BayesDel_noAF	Pathogenic	0.43
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T;.;.;.
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;D;D;D
M_CAP	Benign	0.065	D
MetaRNN	Pathogenic	0.93	D;D;D;D
MetaSVM	Uncertain	-0.072	T
MutationAssessor	Uncertain	2.3	M;M;M;M
PrimateAI	Pathogenic	0.89	D
PROVEAN	Uncertain	-3.9	D;D;D;D
REVEL	Pathogenic	0.81
Sift	Uncertain	0.0010	D;D;D;D
Sift4G	Uncertain	0.0050	D;D;D;D
Polyphen		0.42	B;P;P;P
Vest4		0.94
MutPred		0.82		Loss of stability (P = 0.1152);Loss of stability (P = 0.1152);Loss of stability (P = 0.1152);Loss of stability (P = 0.1152);
MVP		0.34
MPC		0.80
ClinPred		0.98	D
GERP RS		5.8
Varity_R		0.77
gMVP		0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-64933563;