NM_001160372.4:c.1414C>G

Variant names:

• chr8-140360131-G-C
• NM_001160372.4:c.1414C>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001160372.4(TRAPPC9):​c.1414C>G​(p.Arg472Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: 32)
• Consequence: TRAPPC9 NM_001160372.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.03

Genes affected

TRAPPC9 (HGNC:30832): (trafficking protein particle complex subunit 9) This gene encodes a protein that likely plays a role in NF-kappa-B signaling. Mutations in this gene have been associated with autosomal-recessive cognitive disability. Alternatively spliced transcript variants have been described.[provided by RefSeq, Feb 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.827

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAPPC9	NM_001160372.4	c.1414C>G	p.Arg472Gly	missense_variant	Exon 9 of 23	ENST00000438773.4	NP_001153844.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAPPC9	ENST00000438773.4	c.1414C>G	p.Arg472Gly	missense_variant	Exon 9 of 23	1	NM_001160372.4	ENSP00000405060.3
TRAPPC9	ENST00000520857.5	c.943C>G	p.Arg315Gly	missense_variant	Exon 7 of 21	1		ENSP00000430116.1
TRAPPC9	ENST00000648948.2	c.1414C>G	p.Arg472Gly	missense_variant	Exon 9 of 23			ENSP00000498020.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Pathogenic	0.41	D
BayesDel_noAF	Pathogenic	0.35
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.28	T;T;.;T
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.95	.;.;D;D
M_CAP	Benign	0.046	D
MetaRNN	Pathogenic	0.83	D;D;D;D
MetaSVM	Benign	-0.38	T
MutationAssessor	Uncertain	2.3	M;M;.;M
PrimateAI	Pathogenic	0.86	D
PROVEAN	Pathogenic	-5.0	.;D;D;.
REVEL	Uncertain	0.32
Sift	Uncertain	0.0030	.;D;D;.
Sift4G	Uncertain	0.013	.;D;D;.
Polyphen		1.0	D;D;D;D
Vest4		0.93, 0.92
MutPred		0.49		Loss of helix (P = 0.0093);Loss of helix (P = 0.0093);.;Loss of helix (P = 0.0093);
MVP		0.46
MPC		1.5
ClinPred		1.0	D
GERP RS		4.4
Varity_R		0.81
gMVP		0.84

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-141370230;