8-140001539-A-G

Variant names:

• chr8-140001539-A-G
• rs4358783
• NM_001160372.4:c.2700-12703T>C

Variant summary

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

The NM_001160372.4(TRAPPC9):​c.2700-12703T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 152,072 control chromosomes in the GnomAD database, including 11,023 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 0.35 (11023 hom., cov: 32)
• Consequence: TRAPPC9 NM_001160372.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.482
• Publications: 2 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001160372.4. 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.2700-12703T>C		intron	N/A	NP_001153844.1
	TRAPPC9	NM_001374682.1		c.2721-12703T>C		intron	N/A	NP_001361611.1
	TRAPPC9	NM_031466.8		c.2700-12703T>C		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.2700-12703T>C		intron	N/A	ENSP00000405060.3
	TRAPPC9	ENST00000520857.5	TSL:1	c.2229-12703T>C		intron	N/A	ENSP00000430116.1
	TRAPPC9	ENST00000521667.5	TSL:1	n.1105-12703T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52956 AN: 151954 Hom.: 11016 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.438

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.475

Gnomad EAS AF: 0.524

Gnomad SAS AF: 0.497

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.425

Gnomad OTH AF: 0.356

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

GnomAD4 genome AF: 0.348 AC: 52966 AN: 152072 Hom.: 11023 Cov.: 32 AF XY: 0.354 AC XY: 26318 AN XY: 74324

African (AFR) AF: 0.106 AC: 4405 AN: 41536

American (AMR) AF: 0.485 AC: 7410 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.475 AC: 1649 AN: 3470

East Asian (EAS) AF: 0.523 AC: 2708 AN: 5174

South Asian (SAS) AF: 0.498 AC: 2395 AN: 4814

European-Finnish (FIN) AF: 0.400 AC: 4216 AN: 10550

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.425 AC: 28902 AN: 67942

Other (OTH) AF: 0.355 AC: 749 AN: 2112

Alfa AF: 0.417 Hom.: 6836

Bravo AF: 0.345

Asia WGS AF: 0.445 AC: 1545 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	5.7
DANN	Benign	0.75
PhyloP100		-0.48
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: rs4358783; hg19: chr8-141011636;