8-140055634-C-T

Position:

• chr8-140055634-C-T

Variant summary

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

The NM_001160372.4(TRAPPC9):​c.2557-31555G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.719 in 152,126 control chromosomes in the GnomAD database, including 40,241 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 0.72 (40241 hom., cov: 33)
• Consequence: TRAPPC9 NM_001160372.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.184

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.887 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRAPPC9	NM_001160372.4	c.2557-31555G>A		intron_variant		ENST00000438773.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRAPPC9	ENST00000438773.4	c.2557-31555G>A		intron_variant		1	NM_001160372.4	P1

Frequencies

GnomAD3 genomes AF: 0.719 AC: 109277 AN: 152008 Hom.: 40190 Cov.: 33

Gnomad AFR AF: 0.894

Gnomad AMI AF: 0.661

Gnomad AMR AF: 0.650

Gnomad ASJ AF: 0.726

Gnomad EAS AF: 0.567

Gnomad SAS AF: 0.617

Gnomad FIN AF: 0.587

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.666

Gnomad OTH AF: 0.734

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

GnomAD4 genome AF: 0.719 AC: 109377 AN: 152126 Hom.: 40241 Cov.: 33 AF XY: 0.712 AC XY: 52962 AN XY: 74346

Gnomad4 AFR AF: 0.894

Gnomad4 AMR AF: 0.649

Gnomad4 ASJ AF: 0.726

Gnomad4 EAS AF: 0.567

Gnomad4 SAS AF: 0.616

Gnomad4 FIN AF: 0.587

Gnomad4 NFE AF: 0.666

Gnomad4 OTH AF: 0.736

Alfa AF: 0.710 Hom.: 6876

Bravo AF: 0.731

Asia WGS AF: 0.617 AC: 2146 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.0
DANN	Benign	0.41

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: rs11166947; hg19: chr8-141065732;