8-139988737-A-G

Variant names:

• chr8-139988737-A-G
• rs2614718
• NM_001160372.4:c.2799T>C

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0620
• Publications: 9 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: 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

ACMG classification

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.

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

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

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes AF: 0.920 AC: 139913 AN: 152058 Hom.: 64536 Cov.: 32

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.: 39 AF XY: 0.937 AC XY: 645990 AN XY: 689432

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

GnomAD4 genome AF: 0.920 AC: 140015 AN: 152176 Hom.: 64582 Cov.: 32 AF XY: 0.919 AC XY: 68390 AN XY: 74384

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

Alfa AF: 0.935 Hom.: 34897

Bravo AF: 0.904

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	4.1
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

Other links and lift over

dbSNP: rs2614718; hg19: chr8-140998945;