8-139731103-G-C

Variant names:

• chr8-139731103-G-C
• NM_001160372.4:c.3405C>G

Variant summary

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

The NM_001160372.4(TRAPPC9):​c.3405C>G​(p.Cys1135Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,442 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TRAPPC9 NM_001160372.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.43

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 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
TRAPPC9	NM_001160372.4	c.3405C>G	p.Cys1135Trp	missense_variant	Exon 23 of 23	ENST00000438773.4	NP_001153844.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAPPC9	ENST00000438773.4	c.3405C>G	p.Cys1135Trp	missense_variant	Exon 23 of 23	1	NM_001160372.4	ENSP00000405060.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461442 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727028

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	21
DANN	Benign	0.94
DEOGEN2	Benign	0.053	T;T;.;T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.53
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.84	.;.;T;T
M_CAP	Benign	0.038	D
MetaRNN	Uncertain	0.63	D;D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L;L;.;L
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.3	.;N;N;.
REVEL	Benign	0.24
Sift	Benign	0.16	.;T;T;.
Sift4G	Benign	0.075	.;T;T;.
Polyphen		0.98	D;D;D;D
Vest4		0.66, 0.60
MutPred		0.72		Loss of catalytic residue at L1136 (P = 0.0501);Loss of catalytic residue at L1136 (P = 0.0501);.;Loss of catalytic residue at L1136 (P = 0.0501);
MVP		0.23
MPC		0.30
ClinPred		0.63	D
GERP RS		3.1
Varity_R		0.17
gMVP		0.73

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: chr8-140743346;