dbSNP rs2614718: TRAPPC9:p.Gly933Gly (chr8-139988737-A-G) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001160372.4(TRAPPC9):c.2799T>C(p.Gly933Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.934 in 1,549,844 control chromosomes in the GnomAD database, including 677,712 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.92 ( 64582 hom., cov: 32)

Exomes 𝑓: 0.94 ( 613130 hom. )

Consequence

TRAPPC9
NM_001160372.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 8-139988737-A-G is Benign according to our data. Variant chr8-139988737-A-G is described in ClinVar as Benign. ClinVar VariationId is 769201.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

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

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.938 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAPPC9	NM_001160372.4 link	c.2799T>C	p.Gly933Gly	synonymous_variant	Exon 19 of 23	ENST00000438773.4	NP_001153844.1	Q96Q05-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAPPC9	ENST00000438773.4 link	c.2799T>C	p.Gly933Gly	synonymous_variant	Exon 19 of 23	1	NM_001160372.4	ENSP00000405060.3		Q96Q05-1

Frequencies

GnomAD3 genomes

AF:

0.920

AC:

139913

AN:

152058

Hom.:

64536

Cov.:

show subpopulations

Gnomad AFR

AF:

0.898

Gnomad AMI

AF:

0.987

Gnomad AMR

AF:

0.832

Gnomad ASJ

AF:

0.962

Gnomad EAS

AF:

0.934

Gnomad SAS

AF:

0.937

Gnomad FIN

AF:

0.943

Gnomad MID

AF:

0.987

Gnomad NFE

AF:

0.944

Gnomad OTH

AF:

0.918

GnomAD4 exome

AF:

0.936

AC:

1308139

AN:

1397668

Hom.:

613130

Cov.:

AF XY:

0.937

AC XY:

645990

AN XY:

689432

show subpopulations

African (AFR)

AF:

0.901

AC:

28443

AN:

31572

American (AMR)

AF:

0.747

AC:

26652

AN:

35702

Ashkenazi Jewish (ASJ)

AF:

0.964

AC:

24286

AN:

25182

East Asian (EAS)

AF:

0.932

AC:

33302

AN:

35736

South Asian (SAS)

AF:

0.935

AC:

74031

AN:

79186

European-Finnish (FIN)

AF:

0.943

AC:

45887

AN:

48662

Middle Eastern (MID)

AF:

0.982

AC:

5117

AN:

5212

European-Non Finnish (NFE)

AF:

0.942

AC:

1015969

AN:

1078488

Other (OTH)

AF:

0.940

AC:

54452

AN:

57928

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.533

Heterozygous variant carriers

4634

9268

13903

18537

23171

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21184

42368

63552

84736

105920

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.920

AC:

140015

AN:

152176

Hom.:

64582

Cov.:

AF XY:

0.919

AC XY:

68390

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.898

AC:

37279

AN:

41518

American (AMR)

AF:

0.832

AC:

12725

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.962

AC:

3340

AN:

3472

East Asian (EAS)

AF:

0.934

AC:

4798

AN:

5138

South Asian (SAS)

AF:

0.936

AC:

4507

AN:

4816

European-Finnish (FIN)

AF:

0.943

AC:

9994

AN:

10594

Middle Eastern (MID)

AF:

0.986

AC:

290

AN:

294

European-Non Finnish (NFE)

AF:

0.944

AC:

64238

AN:

68024

Other (OTH)

AF:

0.919

AC:

1944

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

558

1115

1673

2230

2788

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

906

1812

2718

3624

4530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.935

Hom.:

34897

Bravo

AF:

0.904

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

May 04, 2022

Mendelics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

4.1

(source)

PhyloP100

-0.062

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over