rs117443048

Variant names:

• chr8-139730896-C-G
• rs117443048
• NM_001160372.4:c.*165G>C

Your query was ambiguous. Multiple possible variants found:

• chr8-139730896-C-G
• chr8-139730896-C-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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=-0.81).
• 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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 31 AR gene

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.*165G>C		3_prime_UTR	Exon 23 of 23	NP_001153844.1	Q96Q05-1
	TRAPPC9	NM_001374682.1		c.*165G>C		3_prime_UTR	Exon 24 of 24	NP_001361611.1
	TRAPPC9	NM_031466.8		c.*165G>C		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.*165G>C		3_prime_UTR	Exon 23 of 23	ENSP00000405060.3	Q96Q05-1
	TRAPPC9	ENST00000520857.5	TSL:1	c.*165G>C		3_prime_UTR	Exon 21 of 21	ENSP00000430116.1	H0YBR0
	TRAPPC9	ENST00000521667.5	TSL:1	n.2017G>C		non_coding_transcript_exon	Exon 12 of 12

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

African (AFR) AF: 0.00491 AC: 79 AN: 16094

American (AMR) AF: 0.0154 AC: 378 AN: 24576

Ashkenazi Jewish (ASJ) AF: 0.0242 AC: 372 AN: 15382

East Asian (EAS) AF: 0.0000312 AC: 1 AN: 32020

South Asian (SAS) AF: 0.00519 AC: 267 AN: 51486

European-Finnish (FIN) AF: 0.00383 AC: 115 AN: 30018

Middle Eastern (MID) AF: 0.0121 AC: 28 AN: 2306

European-Non Finnish (NFE) AF: 0.0241 AC: 10003 AN: 415322

Other (OTH) AF: 0.0212 AC: 676 AN: 31890

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

African (AFR) AF: 0.00395 AC: 164 AN: 41514

American (AMR) AF: 0.0215 AC: 329 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0251 AC: 87 AN: 3468

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5144

South Asian (SAS) AF: 0.00707 AC: 34 AN: 4810

European-Finnish (FIN) AF: 0.00339 AC: 36 AN: 10612

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0241 AC: 1638 AN: 67960

Other (OTH) AF: 0.0227 AC: 48 AN: 2114

Alfa AF: 0.00153 Hom.: 0

Bravo AF: 0.0174

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.3
DANN	Benign	0.51
PhyloP100		-0.053
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Mutation Taster		=100/0	polymorphism

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: rs117443048; hg19: chr8-140743139;