dbSNP rs139848315: TRAPPC9:p.Leu560Val (chr8-140300559-A-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001160372.4(TRAPPC9):c.1678T>G(p.Leu560Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L560L) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TRAPPC9
NM_001160372.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.837

Publications

0 publications found

Variant links:

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: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
intellectual disability-obesity-brain malformations-facial dysmorphism syndrome
Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
autosomal recessive non-syndromic intellectual disability
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

TRAPPC9 links:

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ACMG classification

Classification was made for transcript

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=0.07599324).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAPPC9	NM_001160372.4 link	c.1678T>G	p.Leu560Val	missense_variant	Exon 11 of 23	ENST00000438773.4	NP_001153844.1	Q96Q05-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TRAPPC9	ENST00000438773.4 link	c.1678T>G	p.Leu560Val	missense_variant	Exon 11 of 23	1	NM_001160372.4	ENSP00000405060.3	Q96Q05-1
TRAPPC9	ENST00000520857.5 link	c.1207T>G	p.Leu403Val	missense_variant	Exon 9 of 21	1		ENSP00000430116.1	H0YBR0
TRAPPC9	ENST00000648948.2 link	c.1678T>G	p.Leu560Val	missense_variant	Exon 11 of 23			ENSP00000498020.1	Q96Q05-1
TRAPPC9	ENST00000521167.1 link	n.207T>G		non_coding_transcript_exon_variant	Exon 2 of 5	4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1112012

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.47

DEOGEN2

Benign

0.011

T;T;.;T

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.46

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.81

.;.;T;T

M_CAP

Benign

0.020

MetaRNN

Benign

0.076

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.55

N;N;.;N

PhyloP100

0.84

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.28

.;N;N;.

REVEL

Benign

0.053

Sift

Benign

1.0

.;T;T;.

Sift4G

Benign

0.82

.;T;T;.

Polyphen

0.39

B;B;B;B

Vest4

0.21, 0.20

MutPred

0.31

Loss of helix (P = 0.028);Loss of helix (P = 0.028);.;Loss of helix (P = 0.028);

MVP

0.12

MPC

0.59

ClinPred

0.38

GERP RS

-2.3

Varity_R

0.040

gMVP

0.26

Mutation Taster

=72/28

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over