rs187594197

Variant names:

• chr8-139730529-C-T
• rs187594197
• NM_001160372.4:c.*532G>A

Your query was ambiguous. Multiple possible variants found:

• chr8-139730529-C-T
• chr8-139730529-C-A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_001160372.4(TRAPPC9):​c.*532G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00656 in 159,044 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0065 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0081 (0 hom.)
• Consequence: TRAPPC9 NM_001160372.4 3_prime_UTR
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2 B:1
• Conservation: PhyloP100: -1.54
• Publications: 1 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 8-139730529-C-T is Benign according to our data. Variant chr8-139730529-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 362052.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00649 (987/152168) while in subpopulation NFE AF = 0.0103 (702/67970). AF 95% confidence interval is 0.00969. There are 6 homozygotes in GnomAd4. There are 490 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 6 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.*532G>A		3_prime_UTR	Exon 23 of 23	NP_001153844.1	Q96Q05-1
	TRAPPC9	NM_001374682.1		c.*532G>A		3_prime_UTR	Exon 24 of 24	NP_001361611.1
	TRAPPC9	NM_031466.8		c.*532G>A		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.*532G>A		3_prime_UTR	Exon 23 of 23	ENSP00000405060.3	Q96Q05-1
	TRAPPC9	ENST00000520857.5	TSL:1	c.*532G>A		3_prime_UTR	Exon 21 of 21	ENSP00000430116.1	H0YBR0
	TRAPPC9	ENST00000889106.1		c.*532G>A		3_prime_UTR	Exon 24 of 24	ENSP00000559165.1

Frequencies

GnomAD3 genomes AF: 0.00649 AC: 987 AN: 152050 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00162

Gnomad AMI AF: 0.0165

Gnomad AMR AF: 0.00236

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.0130

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.0103

Gnomad OTH AF: 0.00574

GnomAD4 exome AF: 0.00814 AC: 56 AN: 6876 Hom.: 0 Cov.: 0 AF XY: 0.00701 AC XY: 25 AN XY: 3564

African (AFR) AF: 0.00 AC: 0 AN: 106

American (AMR) AF: 0.00446 AC: 7 AN: 1568

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 48

East Asian (EAS) AF: 0.00 AC: 0 AN: 264

South Asian (SAS) AF: 0.00181 AC: 1 AN: 552

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 98

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 12

European-Non Finnish (NFE) AF: 0.0122 AC: 48 AN: 3946

Other (OTH) AF: 0.00 AC: 0 AN: 282

GnomAD4 genome AF: 0.00649 AC: 987 AN: 152168 Hom.: 6 Cov.: 32 AF XY: 0.00659 AC XY: 490 AN XY: 74400

African (AFR) AF: 0.00161 AC: 67 AN: 41534

American (AMR) AF: 0.00235 AC: 36 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00317 AC: 11 AN: 3472

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5150

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4824

European-Finnish (FIN) AF: 0.0130 AC: 138 AN: 10604

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.0103 AC: 702 AN: 67970

Other (OTH) AF: 0.00568 AC: 12 AN: 2114

Alfa AF: 0.00257 Hom.: 1

Bravo AF: 0.00556

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.51
DANN	Benign	0.37
PhyloP100		-1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism

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: rs187594197; hg19: chr8-140742772;