8-139732090-C-T

Variant names:

• chr8-139732090-C-T
• rs138778665
• NM_001160372.4:c.3168G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP6_Very_Strong BP7

The NM_001160372.4(TRAPPC9):​c.3168G>A​(p.Gly1056Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000233 in 1,605,488 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00024 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00023 (0 hom.)
• Consequence: TRAPPC9 NM_001160372.4 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.20
• Publications: 0 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: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.047).
• BP6: Variant 8-139732090-C-T is Benign according to our data. Variant chr8-139732090-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 437025.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.2 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAPPC9	NM_001160372.4	MANE Select	c.3168G>A	p.Gly1056Gly	synonymous	Exon 22 of 23	NP_001153844.1	Q96Q05-1
	TRAPPC9	NM_001374682.1		c.3189G>A	p.Gly1063Gly	synonymous	Exon 23 of 24	NP_001361611.1
	TRAPPC9	NM_031466.8		c.3168G>A	p.Gly1056Gly	synonymous	Exon 22 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.3168G>A	p.Gly1056Gly	synonymous	Exon 22 of 23	ENSP00000405060.3	Q96Q05-1
	TRAPPC9	ENST00000520857.5	TSL:1	c.2697G>A	p.Gly899Gly	synonymous	Exon 20 of 21	ENSP00000430116.1	H0YBR0
	TRAPPC9	ENST00000521667.5	TSL:1	n.1573G>A		non_coding_transcript_exon	Exon 11 of 12

Frequencies

GnomAD3 genomes AF: 0.000237 AC: 36 AN: 152186 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000134 AC: 31 AN: 231530 AF XY: 0.000175

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000606

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000270

Gnomad OTH exome AF: 0.000177

GnomAD4 exome AF: 0.000233 AC: 338 AN: 1453302 Hom.: 0 Cov.: 32 AF XY: 0.000235 AC XY: 170 AN XY: 722168

African (AFR) AF: 0.00 AC: 0 AN: 33374

American (AMR) AF: 0.0000457 AC: 2 AN: 43718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25910

East Asian (EAS) AF: 0.00 AC: 0 AN: 39314

South Asian (SAS) AF: 0.00 AC: 0 AN: 84596

European-Finnish (FIN) AF: 0.0000191 AC: 1 AN: 52270

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.000291 AC: 323 AN: 1108444

Other (OTH) AF: 0.000200 AC: 12 AN: 59978

GnomAD4 genome AF: 0.000237 AC: 36 AN: 152186 Hom.: 0 Cov.: 33 AF XY: 0.000229 AC XY: 17 AN XY: 74344

African (AFR) AF: 0.000121 AC: 5 AN: 41452

American (AMR) AF: 0.000131 AC: 2 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000358 Hom.: 0

Bravo AF: 0.000295

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Inborn genetic diseases (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	5.6
DANN	Benign	0.91
PhyloP100		-1.2
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs138778665; hg19: chr8-140744333;