Genetic Variant TRAPPC9:p.Gly933Gly (chr8-139988737-A-T) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7

The NM_001160372.4(TRAPPC9):c.2799T>A(p.Gly933Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. G933G) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TRAPPC9
NM_001160372.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0620

Publications

9 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: Likely_benign. The variant received -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP7

Synonymous conserved (PhyloP=-0.062 with no splicing effect.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TRAPPC9	NM_001160372.4	MANE Select	c.2799T>A	p.Gly933Gly	synonymous	Exon 19 of 23	NP_001153844.1
TRAPPC9	NM_001374682.1		c.2820T>A	p.Gly940Gly	synonymous	Exon 20 of 24	NP_001361611.1
TRAPPC9	NM_031466.8		c.2799T>A	p.Gly933Gly	synonymous	Exon 19 of 23	NP_113654.5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TRAPPC9	ENST00000438773.4	TSL:1 MANE Select	c.2799T>A	p.Gly933Gly	synonymous	Exon 19 of 23	ENSP00000405060.3
TRAPPC9	ENST00000520857.5	TSL:1	c.2328T>A	p.Gly776Gly	synonymous	Exon 17 of 21	ENSP00000430116.1
TRAPPC9	ENST00000521667.5	TSL:1	n.1204T>A		non_coding_transcript_exon	Exon 8 of 12

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1397746

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

689472

African (AFR)

AF:

0.00

AC:

AN:

31572

American (AMR)

AF:

0.00

AC:

AN:

35702

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25182

East Asian (EAS)

AF:

0.00

AC:

AN:

35736

South Asian (SAS)

AF:

0.00

AC:

AN:

79186

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48674

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5212

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1078552

Other (OTH)

AF:

0.00

AC:

AN:

57930

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

34897

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

3.7

(source)

PhyloP100

-0.062

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over