5-65637736-G-C

Variant names:

• chr5-65637736-G-C
• rs201726759
• NM_024941.4:c.256G>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_024941.4(TRAPPC13):​c.256G>C​(p.Val86Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000211 in 1,420,484 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V86I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: TRAPPC13 NM_024941.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.24
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.785

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024941.4. 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.256G>C	p.Val86Leu	missense	Exon 4 of 13	NP_079217.2	A5PLN9-1
	TRAPPC13	NM_001093755.2		c.256G>C	p.Val86Leu	missense	Exon 4 of 13	NP_001087224.1	A5PLN9-5
	TRAPPC13	NM_001243737.2		c.256G>C	p.Val86Leu	missense	Exon 4 of 12	NP_001230666.1	A5PLN9-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAPPC13	ENST00000399438.8	TSL:2 MANE Select	c.256G>C	p.Val86Leu	missense	Exon 4 of 13	ENSP00000382367.3	A5PLN9-1
	TRAPPC13	ENST00000438419.6	TSL:1	c.256G>C	p.Val86Leu	missense	Exon 4 of 13	ENSP00000409231.2	A5PLN9-5
	TRAPPC13	ENST00000505553.5	TSL:1	c.256G>C	p.Val86Leu	missense	Exon 4 of 12	ENSP00000423405.1	A5PLN9-4

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000211 AC: 3 AN: 1420484 Hom.: 0 Cov.: 26 AF XY: 0.00000141 AC XY: 1 AN XY: 707578

African (AFR) AF: 0.00 AC: 0 AN: 31360

American (AMR) AF: 0.00 AC: 0 AN: 39202

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25338

East Asian (EAS) AF: 0.00 AC: 0 AN: 38904

South Asian (SAS) AF: 0.00 AC: 0 AN: 81390

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52872

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5632

European-Non Finnish (NFE) AF: 0.00000276 AC: 3 AN: 1087024

Other (OTH) AF: 0.00 AC: 0 AN: 58762

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.056	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.025	D
MetaRNN	Pathogenic	0.79	D
MetaSVM	Benign	-0.50	T
MutationAssessor	Benign	1.2	L
PhyloP100		9.2
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-1.9	N
REVEL	Uncertain	0.41
Sift	Benign	0.056	T
Sift4G	Benign	0.087	T
Polyphen		0.19	B
Vest4		0.76
MutPred		0.83		Gain of catalytic residue at V86 (P = 0.0697)
MVP		0.24
MPC		0.43
ClinPred		0.71	D
GERP RS		5.8
Varity_R		0.27
gMVP		0.55
Mutation Taster		=25/75	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs201726759; hg19: chr5-64933563;