8-139988740-G-T

Variant names:

• chr8-139988740-G-T
• rs145607512
• NM_001160372.4:c.2796C>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001160372.4(TRAPPC9):​c.2796C>A​(p.Ala932Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000716 in 1,397,540 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A932A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: TRAPPC9 NM_001160372.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.728
• Publications: 0 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP7: Synonymous conserved (PhyloP=-0.728 with no splicing effect.

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.2796C>A	p.Ala932Ala	synonymous	Exon 19 of 23	NP_001153844.1
	TRAPPC9	NM_001374682.1		c.2817C>A	p.Ala939Ala	synonymous	Exon 20 of 24	NP_001361611.1
	TRAPPC9	NM_031466.8		c.2796C>A	p.Ala932Ala	synonymous	Exon 19 of 23	NP_113654.5

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAPPC9	ENST00000438773.4	TSL:1 MANE Select	c.2796C>A	p.Ala932Ala	synonymous	Exon 19 of 23	ENSP00000405060.3
	TRAPPC9	ENST00000520857.5	TSL:1	c.2325C>A	p.Ala775Ala	synonymous	Exon 17 of 21	ENSP00000430116.1
	TRAPPC9	ENST00000521667.5	TSL:1	n.1201C>A		non_coding_transcript_exon	Exon 8 of 12

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.16e-7 AC: 1 AN: 1397540 Hom.: 0 Cov.: 34 AF XY: 0.00000145 AC XY: 1 AN XY: 689434

African (AFR) AF: 0.00 AC: 0 AN: 31554

American (AMR) AF: 0.00 AC: 0 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25176

East Asian (EAS) AF: 0.00 AC: 0 AN: 35736

South Asian (SAS) AF: 0.00 AC: 0 AN: 79188

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48824

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5310

European-Non Finnish (NFE) AF: 9.28e-7 AC: 1 AN: 1078128

Other (OTH) AF: 0.00 AC: 0 AN: 57920

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	1.1
DANN	Benign	0.69
PhyloP100		-0.73
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs145607512; hg19: chr8-140998948;