rs6992848

Positions:

• chr8-140140070-T-C
• chr8-140140070-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001160372.4(TRAPPC9):​c.2556+81389A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 151,964 control chromosomes in the GnomAD database, including 7,066 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.29 (7066 hom., cov: 32)
• Consequence: TRAPPC9 NM_001160372.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.08

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRAPPC9	NM_001160372.4	c.2556+81389A>G		intron_variant		ENST00000438773.4	NP_001153844.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRAPPC9	ENST00000438773.4	c.2556+81389A>G		intron_variant		1	NM_001160372.4	ENSP00000405060	P1

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44445 AN: 151846 Hom.: 7052 Cov.: 32

Gnomad AFR AF: 0.393

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.310

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.0122

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.267

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.293 AC: 44511 AN: 151964 Hom.: 7066 Cov.: 32 AF XY: 0.287 AC XY: 21353 AN XY: 74284

Gnomad4 AFR AF: 0.393

Gnomad4 AMR AF: 0.312

Gnomad4 ASJ AF: 0.179

Gnomad4 EAS AF: 0.0122

Gnomad4 SAS AF: 0.152

Gnomad4 FIN AF: 0.223

Gnomad4 NFE AF: 0.278

Gnomad4 OTH AF: 0.262

Alfa AF: 0.273 Hom.: 5549

Bravo AF: 0.302

Asia WGS AF: 0.122 AC: 433 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.13
DANN	Benign	0.14

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

LitVar

Other links and lift over

dbSNP: rs6992848; hg19: chr8-141150169;