8-140059033-A-G

Position:

• chr8-140059033-A-G

Variant summary

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

The NM_001160372.4(TRAPPC9):​c.2557-34954T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.73 in 152,132 control chromosomes in the GnomAD database, including 41,521 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 0.73 (41521 hom., cov: 32)
• Consequence: TRAPPC9 NM_001160372.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.21

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.9 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRAPPC9	NM_001160372.4	c.2557-34954T>C		intron_variant		ENST00000438773.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRAPPC9	ENST00000438773.4	c.2557-34954T>C		intron_variant		1	NM_001160372.4	P1

Frequencies

GnomAD3 genomes AF: 0.730 AC: 110971 AN: 152014 Hom.: 41468 Cov.: 32

Gnomad AFR AF: 0.907

Gnomad AMI AF: 0.661

Gnomad AMR AF: 0.663

Gnomad ASJ AF: 0.735

Gnomad EAS AF: 0.593

Gnomad SAS AF: 0.634

Gnomad FIN AF: 0.596

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.675

Gnomad OTH AF: 0.750

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

GnomAD4 genome AF: 0.730 AC: 111072 AN: 152132 Hom.: 41521 Cov.: 32 AF XY: 0.724 AC XY: 53824 AN XY: 74370

Gnomad4 AFR AF: 0.908

Gnomad4 AMR AF: 0.662

Gnomad4 ASJ AF: 0.735

Gnomad4 EAS AF: 0.593

Gnomad4 SAS AF: 0.633

Gnomad4 FIN AF: 0.596

Gnomad4 NFE AF: 0.675

Gnomad4 OTH AF: 0.751

Alfa AF: 0.671 Hom.: 4533

Bravo AF: 0.742

Asia WGS AF: 0.633 AC: 2203 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	8.1
DANN	Benign	0.40

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: rs756228; hg19: chr8-141069131;