rs6983731

Variant names:

• chr8-140301566-G-A
• rs6983731
• NM_001160372.4:c.1623-952C>T

Variant summary

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

The NM_001160372.4(TRAPPC9):​c.1623-952C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0725 in 152,288 control chromosomes in the GnomAD database, including 464 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 0.073 (464 hom., cov: 33)
• Consequence: TRAPPC9 NM_001160372.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAPPC9	NM_001160372.4	c.1623-952C>T		intron_variant	Intron 10 of 22	ENST00000438773.4	NP_001153844.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAPPC9	ENST00000438773.4	c.1623-952C>T		intron_variant	Intron 10 of 22	1	NM_001160372.4	ENSP00000405060.3
TRAPPC9	ENST00000520857.5	c.1152-952C>T		intron_variant	Intron 8 of 20	1		ENSP00000430116.1
TRAPPC9	ENST00000648948.2	c.1623-952C>T		intron_variant	Intron 10 of 22			ENSP00000498020.1
TRAPPC9	ENST00000521167.1	n.152-952C>T		intron_variant	Intron 1 of 4	4

Frequencies

GnomAD3 genomes AF: 0.0724 AC: 11024 AN: 152170 Hom.: 462 Cov.: 33

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.0490

Gnomad ASJ AF: 0.0831

Gnomad EAS AF: 0.0137

Gnomad SAS AF: 0.0878

Gnomad FIN AF: 0.0348

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0623

Gnomad OTH AF: 0.0738

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

GnomAD4 genome AF: 0.0725 AC: 11041 AN: 152288 Hom.: 464 Cov.: 33 AF XY: 0.0716 AC XY: 5333 AN XY: 74472

African (AFR) AF: 0.111 AC: 4632 AN: 41554

American (AMR) AF: 0.0489 AC: 749 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0831 AC: 288 AN: 3466

East Asian (EAS) AF: 0.0139 AC: 72 AN: 5184

South Asian (SAS) AF: 0.0885 AC: 427 AN: 4824

European-Finnish (FIN) AF: 0.0348 AC: 370 AN: 10622

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0623 AC: 4236 AN: 68014

Other (OTH) AF: 0.0735 AC: 155 AN: 2108

Alfa AF: 0.0659 Hom.: 687

Bravo AF: 0.0747

Asia WGS AF: 0.0640 AC: 222 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.9
DANN	Benign	0.81
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6983731; hg19: chr8-141311665;