8-139730529-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_001160372.4(TRAPPC9):c.*532G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00656 in 159,044 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0065 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0081 (0 hom.)
• Consequence: TRAPPC9 NM_001160372.4 3_prime_UTR
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: -1.54

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 8-139730529-C-T is Benign according to our data. Variant chr8-139730529-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 362052.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=1}.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00649 (987/152168) while in subpopulation NFE AF= 0.0103 (702/67970). AF 95% confidence interval is 0.00969. There are 6 homozygotes in gnomad4. There are 490 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRAPPC9	NM_001160372.4	c.*532G>A		3_prime_UTR_variant	23/23	ENST00000438773.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRAPPC9	ENST00000438773.4	c.*532G>A		3_prime_UTR_variant	23/23	1	NM_001160372.4	P1
TRAPPC9	ENST00000520857.5	c.*532G>A		3_prime_UTR_variant	21/21	1
TRAPPC9	ENST00000648948.2	c.*532G>A		3_prime_UTR_variant	23/23			P1

Frequencies

GnomAD3 genomes AF: 0.00649 AC: 987 AN: 152050 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00162

Gnomad AMI AF: 0.0165

Gnomad AMR AF: 0.00236

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.0130

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.0103

Gnomad OTH AF: 0.00574

GnomAD4 exome AF: 0.00814 AC: 56 AN: 6876 Hom.: 0 Cov.: 0 AF XY: 0.00701 AC XY: 25 AN XY: 3564

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00446

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00181

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0122

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00649 AC: 987 AN: 152168 Hom.: 6 Cov.: 32 AF XY: 0.00659 AC XY: 490 AN XY: 74400

Gnomad4 AFR AF: 0.00161

Gnomad4 AMR AF: 0.00235

Gnomad4 ASJ AF: 0.00317

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.0130

Gnomad4 NFE AF: 0.0103

Gnomad4 OTH AF: 0.00568

Alfa AF: 0.00257 Hom.: 1

Bravo AF: 0.00556

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

Intellectual Disability, Recessive Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2023

TRAPPC9: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.51
Dann	Benign	0.37
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs187594197; hg19: chr8-140742772;