rs2614718

Positions:

• chr8-139988737-A-G
• chr8-139988737-A-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001160372.4(TRAPPC9):​c.2799T>C​(p.Gly933=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.934 in 1,549,844 control chromosomes in the GnomAD database, including 677,712 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.92 (64582 hom., cov: 32)
  • Exomes 𝑓: 0.94 (613130 hom.)
• Consequence: TRAPPC9 NM_001160372.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0620

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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 8-139988737-A-G is Benign according to our data. Variant chr8-139988737-A-G is described in ClinVar as [Benign]. Clinvar id is 769201.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.062 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.938 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRAPPC9	NM_001160372.4	c.2799T>C	p.Gly933=	synonymous_variant	19/23	ENST00000438773.4	NP_001153844.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRAPPC9	ENST00000438773.4	c.2799T>C	p.Gly933=	synonymous_variant	19/23	1	NM_001160372.4	ENSP00000405060	P1

Frequencies

GnomAD3 genomes AF: 0.920 AC: 139913 AN: 152058 Hom.: 64536 Cov.: 32

Gnomad AFR AF: 0.898

Gnomad AMI AF: 0.987

Gnomad AMR AF: 0.832

Gnomad ASJ AF: 0.962

Gnomad EAS AF: 0.934

Gnomad SAS AF: 0.937

Gnomad FIN AF: 0.943

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.944

Gnomad OTH AF: 0.918

GnomAD4 exome AF: 0.936 AC: 1308139 AN: 1397668 Hom.: 613130 Cov.: 39 AF XY: 0.937 AC XY: 645990 AN XY: 689432

Gnomad4 AFR exome AF: 0.901

Gnomad4 AMR exome AF: 0.747

Gnomad4 ASJ exome AF: 0.964

Gnomad4 EAS exome AF: 0.932

Gnomad4 SAS exome AF: 0.935

Gnomad4 FIN exome AF: 0.943

Gnomad4 NFE exome AF: 0.942

Gnomad4 OTH exome AF: 0.940

GnomAD4 genome AF: 0.920 AC: 140015 AN: 152176 Hom.: 64582 Cov.: 32 AF XY: 0.919 AC XY: 68390 AN XY: 74384

Gnomad4 AFR AF: 0.898

Gnomad4 AMR AF: 0.832

Gnomad4 ASJ AF: 0.962

Gnomad4 EAS AF: 0.934

Gnomad4 SAS AF: 0.936

Gnomad4 FIN AF: 0.943

Gnomad4 NFE AF: 0.944

Gnomad4 OTH AF: 0.919

Alfa AF: 0.936 Hom.: 34585

Bravo AF: 0.904

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Mendelics

May 04, 2022

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2614718; hg19: chr8-140998945;