NM_001160372.4:c.731-1563A>G

Variant names:

• chr8-140436803-T-C
• rs1879818
• NM_001160372.4:c.731-1563A>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.731-1563A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.72 in 152,140 control chromosomes in the GnomAD database, including 40,134 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 (40134 hom., cov: 32)
• Consequence: TRAPPC9 NM_001160372.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.30
• Publications: 5 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAPPC9	NM_001160372.4	c.731-1563A>G		intron_variant	Intron 3 of 22	ENST00000438773.4	NP_001153844.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAPPC9	ENST00000438773.4	c.731-1563A>G		intron_variant	Intron 3 of 22	1	NM_001160372.4	ENSP00000405060.3
TRAPPC9	ENST00000520857.5	c.287-1563A>G		intron_variant	Intron 2 of 20	1		ENSP00000430116.1
TRAPPC9	ENST00000648948.2	c.731-1563A>G		intron_variant	Intron 3 of 22			ENSP00000498020.1

Frequencies

GnomAD3 genomes AF: 0.720 AC: 109495 AN: 152022 Hom.: 40088 Cov.: 32

Gnomad AFR AF: 0.637

Gnomad AMI AF: 0.572

Gnomad AMR AF: 0.774

Gnomad ASJ AF: 0.728

Gnomad EAS AF: 0.996

Gnomad SAS AF: 0.882

Gnomad FIN AF: 0.808

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.714

Gnomad OTH AF: 0.729

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

GnomAD4 genome AF: 0.720 AC: 109594 AN: 152140 Hom.: 40134 Cov.: 32 AF XY: 0.729 AC XY: 54204 AN XY: 74378

African (AFR) AF: 0.637 AC: 26426 AN: 41488

American (AMR) AF: 0.775 AC: 11837 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.728 AC: 2528 AN: 3472

East Asian (EAS) AF: 0.996 AC: 5166 AN: 5188

South Asian (SAS) AF: 0.882 AC: 4249 AN: 4820

European-Finnish (FIN) AF: 0.808 AC: 8552 AN: 10586

Middle Eastern (MID) AF: 0.854 AC: 251 AN: 294

European-Non Finnish (NFE) AF: 0.714 AC: 48530 AN: 68006

Other (OTH) AF: 0.732 AC: 1536 AN: 2098

Alfa AF: 0.715 Hom.: 8179

Bravo AF: 0.710

Asia WGS AF: 0.914 AC: 3175 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.83
DANN	Benign	0.35
PhyloP100		-2.3
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: rs1879818; hg19: chr8-141446902;