chr8-139730896-C-G

Position:

• chr8-139730896-C-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.*165G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0185 in 771,216 control chromosomes in the GnomAD database, including 189 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (31 hom., cov: 32)
  • Exomes 𝑓: 0.019 (158 hom.)
• Consequence: TRAPPC9 NM_001160372.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0530

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=-0.81).
• BP6: Variant 8-139730896-C-G is Benign according to our data. Variant chr8-139730896-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1216061.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0157 (2382/152122) while in subpopulation NFE AF= 0.0241 (1638/67960). AF 95% confidence interval is 0.0231. There are 31 homozygotes in gnomad4. There are 1076 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 31 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRAPPC9	NM_001160372.4	c.*165G>C		3_prime_UTR_variant	23/23	ENST00000438773.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRAPPC9	ENST00000438773.4	c.*165G>C		3_prime_UTR_variant	23/23	1	NM_001160372.4	P1
TRAPPC9	ENST00000520857.5	c.*165G>C		3_prime_UTR_variant	21/21	1
TRAPPC9	ENST00000521667.5	n.2017G>C		non_coding_transcript_exon_variant	12/12	1
TRAPPC9	ENST00000648948.2	c.*165G>C		3_prime_UTR_variant	23/23			P1

Frequencies

GnomAD3 genomes AF: 0.0157 AC: 2383 AN: 152004 Hom.: 31 Cov.: 32

Gnomad AFR AF: 0.00396

Gnomad AMI AF: 0.0451

Gnomad AMR AF: 0.0215

Gnomad ASJ AF: 0.0251

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00727

Gnomad FIN AF: 0.00339

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0241

Gnomad OTH AF: 0.0229

GnomAD4 exome AF: 0.0193 AC: 11919 AN: 619094 Hom.: 158 Cov.: 8 AF XY: 0.0189 AC XY: 6055 AN XY: 321198

Gnomad4 AFR exome AF: 0.00491

Gnomad4 AMR exome AF: 0.0154

Gnomad4 ASJ exome AF: 0.0242

Gnomad4 EAS exome AF: 0.0000312

Gnomad4 SAS exome AF: 0.00519

Gnomad4 FIN exome AF: 0.00383

Gnomad4 NFE exome AF: 0.0241

Gnomad4 OTH exome AF: 0.0212

GnomAD4 genome AF: 0.0157 AC: 2382 AN: 152122 Hom.: 31 Cov.: 32 AF XY: 0.0145 AC XY: 1076 AN XY: 74352

Gnomad4 AFR AF: 0.00395

Gnomad4 AMR AF: 0.0215

Gnomad4 ASJ AF: 0.0251

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00707

Gnomad4 FIN AF: 0.00339

Gnomad4 NFE AF: 0.0241

Gnomad4 OTH AF: 0.0227

Alfa AF: 0.00153 Hom.: 0

Bravo AF: 0.0174

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 15, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.3
DANN	Benign	0.51
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs117443048; hg19: chr8-140743139;