rs74414386

Positions:

• chr8-140284041-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001160372.4(TRAPPC9):​c.1982-20A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00269 in 1,613,698 control chromosomes in the GnomAD database, including 88 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (50 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (38 hom.)
• Consequence: TRAPPC9 NM_001160372.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.414

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 8-140284041-T-G is Benign according to our data. Variant chr8-140284041-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 445432.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0136 (2076/152228) while in subpopulation AFR AF= 0.0471 (1955/41538). AF 95% confidence interval is 0.0453. There are 50 homozygotes in gnomad4. There are 1005 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 50 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRAPPC9	NM_001160372.4	c.1982-20A>C		intron_variant		ENST00000438773.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRAPPC9	ENST00000438773.4	c.1982-20A>C		intron_variant		1	NM_001160372.4	P1

Frequencies

GnomAD3 genomes AF: 0.0135 AC: 2054 AN: 152110 Hom.: 47 Cov.: 32

Gnomad AFR AF: 0.0467

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00491

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.0120

GnomAD3 exomes AF: 0.00362 AC: 910 AN: 251120 Hom.: 21 AF XY: 0.00256 AC XY: 347 AN XY: 135742

Gnomad AFR exome AF: 0.0478

Gnomad AMR exome AF: 0.00179

Gnomad ASJ exome AF: 0.00169

Gnomad EAS exome AF: 0.0000545

Gnomad SAS exome AF: 0.000261

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000291

Gnomad OTH exome AF: 0.00212

GnomAD4 exome AF: 0.00155 AC: 2263 AN: 1461470 Hom.: 38 Cov.: 33 AF XY: 0.00135 AC XY: 981 AN XY: 727042

Gnomad4 AFR exome AF: 0.0473

Gnomad4 AMR exome AF: 0.00190

Gnomad4 ASJ exome AF: 0.00115

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000359

Gnomad4 FIN exome AF: 0.0000188

Gnomad4 NFE exome AF: 0.000238

Gnomad4 OTH exome AF: 0.00359

GnomAD4 genome AF: 0.0136 AC: 2076 AN: 152228 Hom.: 50 Cov.: 32 AF XY: 0.0135 AC XY: 1005 AN XY: 74420

Gnomad4 AFR AF: 0.0471

Gnomad4 AMR AF: 0.00491

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.0118

Alfa AF: 0.00753 Hom.: 3

Bravo AF: 0.0156

Asia WGS AF: 0.00462 AC: 16 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 14, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jul 28, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.28
DANN	Benign	0.35

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

Publications

LitVar

Other links and lift over

dbSNP: rs74414386; hg19: chr8-141294140;