8-140059033-A-G

Variant names:

• chr8-140059033-A-G
• rs756228
• NM_001160372.4:c.2557-34954T>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.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
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.9 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.2557-34954T>C		intron	N/A	NP_001153844.1
	TRAPPC9	NM_001374682.1		c.2578-34954T>C		intron	N/A	NP_001361611.1
	TRAPPC9	NM_031466.8		c.2557-34954T>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.2557-34954T>C		intron	N/A	ENSP00000405060.3
	TRAPPC9	ENST00000520857.5	TSL:1	c.2086-34954T>C		intron	N/A	ENSP00000430116.1
	TRAPPC9	ENST00000521667.5	TSL:1	n.962-34954T>C		intron	N/A

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

African (AFR) AF: 0.908 AC: 37678 AN: 41518

American (AMR) AF: 0.662 AC: 10118 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.735 AC: 2552 AN: 3472

East Asian (EAS) AF: 0.593 AC: 3069 AN: 5176

South Asian (SAS) AF: 0.633 AC: 3048 AN: 4814

European-Finnish (FIN) AF: 0.596 AC: 6302 AN: 10574

Middle Eastern (MID) AF: 0.844 AC: 248 AN: 294

European-Non Finnish (NFE) AF: 0.675 AC: 45870 AN: 67972

Other (OTH) AF: 0.751 AC: 1584 AN: 2108

Alfa AF: 0.681 Hom.: 4852

Bravo AF: 0.742

Asia WGS AF: 0.633 AC: 2203 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	8.1
DANN	Benign	0.40
PhyloP100		1.2
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: rs756228; hg19: chr8-141069131;