chr8-140055634-C-T

Variant names:

• chr8-140055634-C-T
• rs11166947
• NM_001160372.4:c.2557-31555G>A

Variant summary

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

The NM_001374682.1(TRAPPC9):​c.2578-31555G>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_001374682.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.184
• Publications: 4 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

ENSG00000289741 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001374682.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAPPC9	NM_001160372.4	MANE Select	c.2557-31555G>A		intron	N/A	NP_001153844.1
	TRAPPC9	NM_001374682.1		c.2578-31555G>A		intron	N/A	NP_001361611.1
	TRAPPC9	NM_031466.8		c.2557-31555G>A		intron	N/A	NP_113654.5

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAPPC9	ENST00000438773.4	TSL:1 MANE Select	c.2557-31555G>A		intron	N/A	ENSP00000405060.3
	TRAPPC9	ENST00000520857.5	TSL:1	c.2086-31555G>A		intron	N/A	ENSP00000430116.1
	TRAPPC9	ENST00000521667.5	TSL:1	n.962-31555G>A		intron	N/A

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

African (AFR) AF: 0.894 AC: 37157 AN: 41554

American (AMR) AF: 0.649 AC: 9927 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.726 AC: 2520 AN: 3470

East Asian (EAS) AF: 0.567 AC: 2928 AN: 5162

South Asian (SAS) AF: 0.616 AC: 2971 AN: 4822

European-Finnish (FIN) AF: 0.587 AC: 6196 AN: 10564

Middle Eastern (MID) AF: 0.833 AC: 245 AN: 294

European-Non Finnish (NFE) AF: 0.666 AC: 45280 AN: 67956

Other (OTH) AF: 0.736 AC: 1550 AN: 2106

Alfa AF: 0.715 Hom.: 7186

Bravo AF: 0.731

Asia WGS AF: 0.617 AC: 2146 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.0
DANN	Benign	0.41
PhyloP100		-0.18
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: rs11166947; hg19: chr8-141065732;