chr8-140451348-C-A

Variant names:

• chr8-140451348-C-A
• NM_001160372.4:c.26G>T

Variant summary

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

The NM_001160372.4(TRAPPC9):​c.26G>T​(p.Cys9Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000344 in 1,452,872 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: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: TRAPPC9 NM_001160372.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.80

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, 0.775

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAPPC9	NM_001160372.4	c.26G>T	p.Cys9Phe	missense_variant	Exon 2 of 23	ENST00000438773.4	NP_001153844.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAPPC9	ENST00000438773.4	c.26G>T	p.Cys9Phe	missense_variant	Exon 2 of 23	1	NM_001160372.4	ENSP00000405060.3
TRAPPC9	ENST00000648948.2	c.26G>T	p.Cys9Phe	missense_variant	Exon 2 of 23			ENSP00000498020.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000344 AC: 5 AN: 1452872 Hom.: 0 Cov.: 34 AF XY: 0.00000415 AC XY: 3 AN XY: 723030

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000450

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Pathogenic	0.41	D
BayesDel_noAF	Pathogenic	0.35
CADD	Pathogenic	27
DANN	Uncertain	0.98
DEOGEN2	Benign	0.050	T;T;.;T
Eigen	Uncertain	0.64
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	.;.;D;D
M_CAP	Benign	0.013	T
MetaRNN	Pathogenic	0.78	D;D;D;D
MetaSVM	Benign	-0.38	T
MutationAssessor	Benign	1.8	L;L;.;L
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-2.4	.;N;D;.
REVEL	Uncertain	0.41
Sift	Benign	0.047	.;D;D;.
Sift4G	Uncertain	0.024	.;D;D;.
Polyphen		1.0	D;D;D;D
Vest4		0.87, 0.91
MutPred		0.40		Loss of catalytic residue at M7 (P = 2e-04);Loss of catalytic residue at M7 (P = 2e-04);.;Loss of catalytic residue at M7 (P = 2e-04);
MVP		0.62
MPC		1.8
ClinPred		0.97	D
GERP RS		5.3
Varity_R		0.47
gMVP		0.70

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: chr8-141461447;