8-139972422-T-C

Variant names:

• chr8-139972422-T-C
• rs6981165
• NM_001160372.4:c.2810+16304A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001160372.4(TRAPPC9):​c.2810+16304A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 152,182 control chromosomes in the GnomAD database, including 1,800 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 0.13 (1800 hom., cov: 32)
• Consequence: TRAPPC9 NM_001160372.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.156
• Publications: 1 publications found

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]

TRAPPC9 Gene-Disease associations (from GenCC):

• intellectual disability, autosomal recessive 13

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• intellectual disability-obesity-brain malformations-facial dysmorphism syndrome

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAPPC9	NM_001160372.4	c.2810+16304A>G		intron_variant	Intron 19 of 22	ENST00000438773.4	NP_001153844.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAPPC9	ENST00000438773.4	c.2810+16304A>G		intron_variant	Intron 19 of 22	1	NM_001160372.4	ENSP00000405060.3

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19736 AN: 152064 Hom.: 1796 Cov.: 32

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.0631

Gnomad EAS AF: 0.410

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.0813

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.0814

Gnomad OTH AF: 0.150

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

GnomAD4 genome AF: 0.130 AC: 19754 AN: 152182 Hom.: 1800 Cov.: 32 AF XY: 0.131 AC XY: 9736 AN XY: 74420

African (AFR) AF: 0.202 AC: 8371 AN: 41490

American (AMR) AF: 0.112 AC: 1710 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0631 AC: 219 AN: 3472

East Asian (EAS) AF: 0.410 AC: 2117 AN: 5166

South Asian (SAS) AF: 0.110 AC: 531 AN: 4828

European-Finnish (FIN) AF: 0.0813 AC: 863 AN: 10614

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.0814 AC: 5536 AN: 68000

Other (OTH) AF: 0.149 AC: 314 AN: 2110

Alfa AF: 0.100 Hom.: 3977

Bravo AF: 0.139

Asia WGS AF: 0.236 AC: 819 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.5
DANN	Benign	0.54
PhyloP100		-0.16
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6981165; hg19: chr8-140982636;