rs6983731

Positions:

• chr8-140301566-G-A

Variant summary

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

The NM_001160372.4(TRAPPC9):​c.1623-952C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0725 in 152,288 control chromosomes in the GnomAD database, including 464 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 0.073 (464 hom., cov: 33)
• Consequence: TRAPPC9 NM_001160372.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRAPPC9	NM_001160372.4	c.1623-952C>T		intron_variant		ENST00000438773.4	NP_001153844.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRAPPC9	ENST00000438773.4	c.1623-952C>T		intron_variant		1	NM_001160372.4	ENSP00000405060	P1
TRAPPC9	ENST00000520857.5	c.1153-952C>T		intron_variant		1		ENSP00000430116
TRAPPC9	ENST00000648948.2	c.1623-952C>T		intron_variant				ENSP00000498020	P1
TRAPPC9	ENST00000521167.1	n.152-952C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0724 AC: 11024 AN: 152170 Hom.: 462 Cov.: 33

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.0490

Gnomad ASJ AF: 0.0831

Gnomad EAS AF: 0.0137

Gnomad SAS AF: 0.0878

Gnomad FIN AF: 0.0348

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0623

Gnomad OTH AF: 0.0738

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

GnomAD4 genome AF: 0.0725 AC: 11041 AN: 152288 Hom.: 464 Cov.: 33 AF XY: 0.0716 AC XY: 5333 AN XY: 74472

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.0489

Gnomad4 ASJ AF: 0.0831

Gnomad4 EAS AF: 0.0139

Gnomad4 SAS AF: 0.0885

Gnomad4 FIN AF: 0.0348

Gnomad4 NFE AF: 0.0623

Gnomad4 OTH AF: 0.0735

Alfa AF: 0.0647 Hom.: 463

Bravo AF: 0.0747

Asia WGS AF: 0.0640 AC: 222 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.9
DANN	Benign	0.81

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: rs6983731; hg19: chr8-141311665;