rs4317547

Variant names:

• chr8-140274999-A-C
• rs4317547
• NM_001160372.4:c.2278+659T>G

Your query was ambiguous. Multiple possible variants found:

• chr8-140274999-A-C
• chr8-140274999-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001160372.4(TRAPPC9):​c.2278+659T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.736 in 152,072 control chromosomes in the GnomAD database, including 42,493 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.74 (42493 hom., cov: 32)
• Consequence: TRAPPC9 NM_001160372.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.963
• Publications: 2 publications found

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]

TRAPPC9 Gene-Disease associations (from GenCC):

• intellectual disability, autosomal recessive 13

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• intellectual disability-obesity-brain malformations-facial dysmorphism syndrome

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000308537 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.866 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAPPC9	NM_001160372.4	c.2278+659T>G		intron_variant	Intron 15 of 22	ENST00000438773.4	NP_001153844.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAPPC9	ENST00000438773.4	c.2278+659T>G		intron_variant	Intron 15 of 22	1	NM_001160372.4	ENSP00000405060.3

Frequencies

GnomAD3 genomes AF: 0.736 AC: 111872 AN: 151954 Hom.: 42439 Cov.: 32

Gnomad AFR AF: 0.874

Gnomad AMI AF: 0.816

Gnomad AMR AF: 0.623

Gnomad ASJ AF: 0.838

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.625

Gnomad FIN AF: 0.624

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.732

Gnomad OTH AF: 0.751

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.736 AC: 111987 AN: 152072 Hom.: 42493 Cov.: 32 AF XY: 0.725 AC XY: 53890 AN XY: 74336

African (AFR) AF: 0.874 AC: 36236 AN: 41474

American (AMR) AF: 0.623 AC: 9512 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.838 AC: 2911 AN: 3472

East Asian (EAS) AF: 0.266 AC: 1377 AN: 5176

South Asian (SAS) AF: 0.626 AC: 3012 AN: 4814

European-Finnish (FIN) AF: 0.624 AC: 6590 AN: 10562

Middle Eastern (MID) AF: 0.833 AC: 245 AN: 294

European-Non Finnish (NFE) AF: 0.732 AC: 49769 AN: 67982

Other (OTH) AF: 0.754 AC: 1592 AN: 2112

Alfa AF: 0.738 Hom.: 52055

Bravo AF: 0.743

Asia WGS AF: 0.491 AC: 1707 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.9
DANN	Benign	0.62
PhyloP100		-0.96
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4317547; hg19: chr8-141285098;