8-139730957-G-A

Position:

• chr8-139730957-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001160372.4(TRAPPC9):​c.*104C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 1,280,028 control chromosomes in the GnomAD database, including 19,666 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (3245 hom., cov: 32)
  • Exomes 𝑓: 0.17 (16421 hom.)
• Consequence: TRAPPC9 NM_001160372.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.850

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 8-139730957-G-A is Benign according to our data. Variant chr8-139730957-G-A is described in ClinVar as [Benign]. Clinvar id is 362057.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRAPPC9	NM_001160372.4	c.*104C>T		3_prime_UTR_variant	23/23	ENST00000438773.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRAPPC9	ENST00000438773.4	c.*104C>T		3_prime_UTR_variant	23/23	1	NM_001160372.4	P1

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29568 AN: 151716 Hom.: 3243 Cov.: 32

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.0563

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.181

GnomAD4 exome AF: 0.166 AC: 186802 AN: 1128194 Hom.: 16421 Cov.: 15 AF XY: 0.167 AC XY: 94209 AN XY: 562780

Gnomad4 AFR exome AF: 0.304

Gnomad4 AMR exome AF: 0.103

Gnomad4 ASJ exome AF: 0.185

Gnomad4 EAS exome AF: 0.119

Gnomad4 SAS exome AF: 0.224

Gnomad4 FIN exome AF: 0.144

Gnomad4 NFE exome AF: 0.161

Gnomad4 OTH exome AF: 0.178

GnomAD4 genome AF: 0.195 AC: 29597 AN: 151834 Hom.: 3245 Cov.: 32 AF XY: 0.191 AC XY: 14181 AN XY: 74196

Gnomad4 AFR AF: 0.305

Gnomad4 AMR AF: 0.142

Gnomad4 ASJ AF: 0.176

Gnomad4 EAS AF: 0.106

Gnomad4 SAS AF: 0.233

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.155

Gnomad4 OTH AF: 0.180

Alfa AF: 0.165 Hom.: 2105

Bravo AF: 0.196

Asia WGS AF: 0.202 AC: 703 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Intellectual Disability, Recessive Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.76
DANN	Benign	0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs199226; hg19: chr8-140743200;