5-65636008-G-C

Variant names:

• chr5-65636008-G-C
• rs914594424
• NM_024941.4:c.180G>C

Variant summary

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

The NM_024941.4(TRAPPC13):​c.180G>C​(p.Met60Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,200 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M60V) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: TRAPPC13 NM_024941.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.34
• 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=0.24869221).

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.180G>C	p.Met60Ile	missense	Exon 3 of 13	NP_079217.2	A5PLN9-1
	TRAPPC13	NM_001093755.2		c.180G>C	p.Met60Ile	missense	Exon 3 of 13	NP_001087224.1	A5PLN9-5
	TRAPPC13	NM_001243737.2		c.180G>C	p.Met60Ile	missense	Exon 3 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.180G>C	p.Met60Ile	missense	Exon 3 of 13	ENSP00000382367.3	A5PLN9-1
	TRAPPC13	ENST00000438419.6	TSL:1	c.180G>C	p.Met60Ile	missense	Exon 3 of 13	ENSP00000409231.2	A5PLN9-5
	TRAPPC13	ENST00000505553.5	TSL:1	c.180G>C	p.Met60Ile	missense	Exon 3 of 12	ENSP00000423405.1	A5PLN9-4

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152200 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152200 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74344

African (AFR) AF: 0.0000241 AC: 1 AN: 41442

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5204

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68044

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Uncertain	0.044	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	T
Eigen	Benign	0.016
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.46	N
PhyloP100		7.3
PrimateAI	Pathogenic	0.80	D
PROVEAN	Benign	-0.62	N
REVEL	Benign	0.21
Sift	Benign	0.069	T
Sift4G	Benign	0.27	T
Polyphen		0.0	B
Vest4		0.47
MutPred		0.34		Gain of catalytic residue at L65 (P = 0.0829)
MVP		0.16
MPC		0.43
ClinPred		0.81	D
GERP RS		5.7
Varity_R		0.18
gMVP		0.41
Mutation Taster		=88/12	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: rs914594424; hg19: chr5-64931835;