rs551407866

Variant names:

• chr8-140300544-C-A
• NM_001160372.4:c.1693G>T

Your query was ambiguous. Multiple possible variants found:

• chr8-140300544-C-A
• chr8-140300544-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001160372.4(TRAPPC9):​c.1693G>T​(p.Val565Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: TRAPPC9 NM_001160372.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0560

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.037255973).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAPPC9	NM_001160372.4	c.1693G>T	p.Val565Leu	missense_variant	Exon 11 of 23	ENST00000438773.4	NP_001153844.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAPPC9	ENST00000438773.4	c.1693G>T	p.Val565Leu	missense_variant	Exon 11 of 23	1	NM_001160372.4	ENSP00000405060.3
TRAPPC9	ENST00000520857.5	c.1222G>T	p.Val408Leu	missense_variant	Exon 9 of 21	1		ENSP00000430116.1
TRAPPC9	ENST00000648948.2	c.1693G>T	p.Val565Leu	missense_variant	Exon 11 of 23			ENSP00000498020.1
TRAPPC9	ENST00000521167.1	n.222G>T		non_coding_transcript_exon_variant	Exon 2 of 5	4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461888 Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4 AN XY: 727242

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: 0.00000540

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	0.10
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	7.6
DANN	Benign	0.85
DEOGEN2	Benign	0.020	T;T;.;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.79	.;.;T;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.037	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.41	N;N;.;N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.44	.;N;N;.
REVEL	Benign	0.030
Sift	Benign	0.34	.;T;T;.
Sift4G	Benign	0.73	.;T;T;.
Polyphen		0.0	B;B;B;B
Vest4		0.066, 0.095
MutPred		0.35		Loss of ubiquitination at K568 (P = 0.0709);Loss of ubiquitination at K568 (P = 0.0709);.;Loss of ubiquitination at K568 (P = 0.0709);
MVP		0.048
MPC		0.50
ClinPred		0.43	T
GERP RS		-1.4
Varity_R		0.024
gMVP		0.16

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: chr8-141310643;