chr8-139730686-G-A

Position:

• chr8-139730686-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001160372.4(TRAPPC9):​c.*375C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00908 in 255,454 control chromosomes in the GnomAD database, including 95 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.010 (57 hom., cov: 32)
  • Exomes 𝑓: 0.0076 (38 hom.)
• Consequence: TRAPPC9 NM_001160372.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.139

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 8-139730686-G-A is Benign according to our data. Variant chr8-139730686-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 362053.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRAPPC9	NM_001160372.4	c.*375C>T		3_prime_UTR_variant	23/23	ENST00000438773.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRAPPC9	ENST00000438773.4	c.*375C>T		3_prime_UTR_variant	23/23	1	NM_001160372.4	P1
TRAPPC9	ENST00000520857.5	c.*375C>T		3_prime_UTR_variant	21/21	1
TRAPPC9	ENST00000648948.2	c.*375C>T		3_prime_UTR_variant	23/23			P1

Frequencies

GnomAD3 genomes AF: 0.0100 AC: 1528 AN: 152168 Hom.: 57 Cov.: 32

Gnomad AFR AF: 0.00229

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0679

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0658

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.00907

GnomAD4 exome AF: 0.00764 AC: 788 AN: 103168 Hom.: 38 Cov.: 0 AF XY: 0.00765 AC XY: 406 AN XY: 53090

Gnomad4 AFR exome AF: 0.000700

Gnomad4 AMR exome AF: 0.0589

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0748

Gnomad4 SAS exome AF: 0.000717

Gnomad4 FIN exome AF: 0.000457

Gnomad4 NFE exome AF: 0.000315

Gnomad4 OTH exome AF: 0.00500

GnomAD4 genome AF: 0.0101 AC: 1532 AN: 152286 Hom.: 57 Cov.: 32 AF XY: 0.0118 AC XY: 876 AN XY: 74454

Gnomad4 AFR AF: 0.00229

Gnomad4 AMR AF: 0.0680

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0663

Gnomad4 SAS AF: 0.00269

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.000323

Gnomad4 OTH AF: 0.00898

Alfa AF: 0.00381 Hom.: 0

Bravo AF: 0.0140

Asia WGS AF: 0.0250 AC: 88 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Intellectual Disability, Recessive Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.5
DANN	Benign	0.44

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: rs79408026; hg19: chr8-140742929;