chr5-65660838-G-A

Variant names:

• chr5-65660838-G-A
• rs375637923
• NM_024941.4:c.838G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_024941.4(TRAPPC13):​c.838G>A​(p.Val280Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRAPPC13 NM_024941.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.52

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAPPC13	NM_024941.4	c.838G>A	p.Val280Ile	missense_variant	Exon 10 of 13	ENST00000399438.8	NP_079217.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAPPC13	ENST00000399438.8	c.838G>A	p.Val280Ile	missense_variant	Exon 10 of 13	2	NM_024941.4	ENSP00000382367.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

EpiCase AF: 0.0000546

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Uncertain	0.078	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.019	T;.;.;.
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.88	D;D;D;D
M_CAP	Benign	0.0044	T
MetaRNN	Uncertain	0.50	T;T;T;T
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	1.6	L;L;.;.
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.49	N;N;N;N
REVEL	Benign	0.26
Sift	Benign	0.19	T;T;T;T
Sift4G	Benign	0.21	T;T;T;T
Polyphen		0.55	P;B;B;B
Vest4		0.58
MutPred		0.74		Gain of catalytic residue at L285 (P = 0.0363);Gain of catalytic residue at L285 (P = 0.0363);.;.;
MVP		0.15
MPC		0.53
ClinPred		0.93	D
GERP RS		5.1
Varity_R		0.14
gMVP		0.35

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: rs375637923; hg19: chr5-64956665;