8-139730957-G-A

Variant names:

• chr8-139730957-G-A
• rs199226
• NM_001160372.4:c.*104C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001160372.4(TRAPPC9):​c.*104C>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 0.169 in 1,280,028 control chromosomes in the GnomAD database, including 19,666 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (3245 hom., cov: 32)
  • Exomes 𝑓: 0.17 (16421 hom.)
• Consequence: TRAPPC9 NM_001160372.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.850
• Publications: 8 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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• intellectual disability-obesity-brain malformations-facial dysmorphism syndrome

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

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 8-139730957-G-A is Benign according to our data. Variant chr8-139730957-G-A is described in ClinVar as Benign. ClinVar VariationId is 362057.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001160372.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAPPC9	NM_001160372.4	MANE Select	c.*104C>T		3_prime_UTR	Exon 23 of 23	NP_001153844.1	Q96Q05-1
	TRAPPC9	NM_001374682.1		c.*104C>T		3_prime_UTR	Exon 24 of 24	NP_001361611.1
	TRAPPC9	NM_031466.8		c.*104C>T		3_prime_UTR	Exon 23 of 23	NP_113654.5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAPPC9	ENST00000438773.4	TSL:1 MANE Select	c.*104C>T		3_prime_UTR	Exon 23 of 23	ENSP00000405060.3	Q96Q05-1
	TRAPPC9	ENST00000520857.5	TSL:1	c.*104C>T		3_prime_UTR	Exon 21 of 21	ENSP00000430116.1	H0YBR0
	TRAPPC9	ENST00000521667.5	TSL:1	n.1956C>T		non_coding_transcript_exon	Exon 12 of 12

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29568 AN: 151716 Hom.: 3243 Cov.: 32

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.0563

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.181

GnomAD4 exome AF: 0.166 AC: 186802 AN: 1128194 Hom.: 16421 Cov.: 15 AF XY: 0.167 AC XY: 94209 AN XY: 562780

African (AFR) AF: 0.304 AC: 8152 AN: 26852

American (AMR) AF: 0.103 AC: 3507 AN: 34088

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 3885 AN: 20948

East Asian (EAS) AF: 0.119 AC: 4215 AN: 35376

South Asian (SAS) AF: 0.224 AC: 15229 AN: 67870

European-Finnish (FIN) AF: 0.144 AC: 5237 AN: 36300

Middle Eastern (MID) AF: 0.201 AC: 702 AN: 3500

European-Non Finnish (NFE) AF: 0.161 AC: 137134 AN: 854136

Other (OTH) AF: 0.178 AC: 8741 AN: 49124

GnomAD4 genome AF: 0.195 AC: 29597 AN: 151834 Hom.: 3245 Cov.: 32 AF XY: 0.191 AC XY: 14181 AN XY: 74196

African (AFR) AF: 0.305 AC: 12631 AN: 41376

American (AMR) AF: 0.142 AC: 2173 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 610 AN: 3472

East Asian (EAS) AF: 0.106 AC: 542 AN: 5124

South Asian (SAS) AF: 0.233 AC: 1117 AN: 4788

European-Finnish (FIN) AF: 0.144 AC: 1521 AN: 10556

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.155 AC: 10507 AN: 67932

Other (OTH) AF: 0.180 AC: 379 AN: 2106

Alfa AF: 0.167 Hom.: 2554

Bravo AF: 0.196

Asia WGS AF: 0.202 AC: 703 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Intellectual Disability, Recessive (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.76
DANN	Benign	0.45
PhyloP100		-0.85
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs199226; hg19: chr8-140743200;