chr8-139951684-T-C

Variant names:

• chr8-139951684-T-C
• rs881378
• NM_001160372.4:c.2810+37042A>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.2810+37042A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.892 in 152,268 control chromosomes in the GnomAD database, including 60,778 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 0.89 (60778 hom., cov: 33)
• Consequence: TRAPPC9 NM_001160372.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.254
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.964 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAPPC9	NM_001160372.4	c.2810+37042A>G		intron_variant	Intron 19 of 22	ENST00000438773.4	NP_001153844.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAPPC9	ENST00000438773.4	c.2810+37042A>G		intron_variant	Intron 19 of 22	1	NM_001160372.4	ENSP00000405060.3

Frequencies

GnomAD3 genomes AF: 0.892 AC: 135779 AN: 152150 Hom.: 60735 Cov.: 33

Gnomad AFR AF: 0.911

Gnomad AMI AF: 0.979

Gnomad AMR AF: 0.797

Gnomad ASJ AF: 0.941

Gnomad EAS AF: 0.986

Gnomad SAS AF: 0.896

Gnomad FIN AF: 0.888

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.891

Gnomad OTH AF: 0.906

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

GnomAD4 genome AF: 0.892 AC: 135878 AN: 152268 Hom.: 60778 Cov.: 33 AF XY: 0.892 AC XY: 66403 AN XY: 74434

African (AFR) AF: 0.911 AC: 37839 AN: 41548

American (AMR) AF: 0.797 AC: 12191 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.941 AC: 3268 AN: 3472

East Asian (EAS) AF: 0.986 AC: 5109 AN: 5180

South Asian (SAS) AF: 0.894 AC: 4313 AN: 4824

European-Finnish (FIN) AF: 0.888 AC: 9417 AN: 10600

Middle Eastern (MID) AF: 0.990 AC: 291 AN: 294

European-Non Finnish (NFE) AF: 0.891 AC: 60640 AN: 68026

Other (OTH) AF: 0.907 AC: 1917 AN: 2114

Alfa AF: 0.874 Hom.: 10795

Bravo AF: 0.883

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.2
PhyloP100		0.25

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs881378; hg19: chr8-140963979;