rs797046048

Variant names:

• chr8-140300492-C-G
• rs797046048
• NM_001160372.4:c.1745G>C

Variant summary

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

The NM_001160372.4(TRAPPC9):​c.1745G>C​(p.Gly582Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TRAPPC9 NM_001160372.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.29
• Publications: 1 publications found

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]

TRAPPC9 Gene-Disease associations (from GenCC):

• intellectual disability, autosomal recessive 13

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• intellectual disability-obesity-brain malformations-facial dysmorphism syndrome

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

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=0.22817141).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001160372.4. 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
	TRAPPC9	NM_001160372.4	MANE Select	c.1745G>C	p.Gly582Ala	missense	Exon 11 of 23	NP_001153844.1	Q96Q05-1
	TRAPPC9	NM_001374682.1		c.1766G>C	p.Gly589Ala	missense	Exon 12 of 24	NP_001361611.1
	TRAPPC9	NM_031466.8		c.1745G>C	p.Gly582Ala	missense	Exon 11 of 23	NP_113654.5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAPPC9	ENST00000438773.4	TSL:1 MANE Select	c.1745G>C	p.Gly582Ala	missense	Exon 11 of 23	ENSP00000405060.3	Q96Q05-1
	TRAPPC9	ENST00000520857.5	TSL:1	c.1274G>C	p.Gly425Ala	missense	Exon 9 of 21	ENSP00000430116.1	H0YBR0
	TRAPPC9	ENST00000889106.1		c.1766G>C	p.Gly589Ala	missense	Exon 12 of 24	ENSP00000559165.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.092	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.020	T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	1.7	L
PhyloP100		5.3
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.64	N
REVEL	Benign	0.071
Sift	Benign	0.16	T
Sift4G	Benign	0.78	T
Polyphen		0.52	P
Vest4		0.29
MutPred		0.27		Gain of helix (P = 0.0078)
MVP		0.40
MPC		1.3
ClinPred		0.85	D
GERP RS		4.8
Varity_R		0.12
gMVP		0.47
Mutation Taster		=84/16	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs797046048; hg19: chr8-141310591;