rs12549048

Variant names:

• chr8-140300545-G-A
• rs12549048
• NM_001160372.4:c.1692C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-140300545-G-A
• chr8-140300545-G-T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001160372.4(TRAPPC9):​c.1692C>T​(p.Asn564Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 1,613,968 control chromosomes in the GnomAD database, including 44,741 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (4965 hom., cov: 33)
  • Exomes 𝑓: 0.21 (39776 hom.)
• Consequence: TRAPPC9 NM_001160372.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.239
• Publications: 20 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.017).
• BP6: Variant 8-140300545-G-A is Benign according to our data. Variant chr8-140300545-G-A is described in ClinVar as Benign. ClinVar VariationId is 130622.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.239 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.613 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.1692C>T	p.Asn564Asn	synonymous	Exon 11 of 23	NP_001153844.1	Q96Q05-1
	TRAPPC9	NM_001374682.1		c.1713C>T	p.Asn571Asn	synonymous	Exon 12 of 24	NP_001361611.1
	TRAPPC9	NM_031466.8		c.1692C>T	p.Asn564Asn	synonymous	Exon 11 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.1692C>T	p.Asn564Asn	synonymous	Exon 11 of 23	ENSP00000405060.3	Q96Q05-1
	TRAPPC9	ENST00000520857.5	TSL:1	c.1221C>T	p.Asn407Asn	synonymous	Exon 9 of 21	ENSP00000430116.1	H0YBR0
	TRAPPC9	ENST00000889106.1		c.1713C>T	p.Asn571Asn	synonymous	Exon 12 of 24	ENSP00000559165.1

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35846 AN: 152036 Hom.: 4957 Cov.: 33

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.631

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.124

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.213

GnomAD2 exomes AF: 0.276 AC: 69455 AN: 251486 AF XY: 0.272

Gnomad AFR exome AF: 0.235

Gnomad AMR exome AF: 0.404

Gnomad ASJ exome AF: 0.178

Gnomad EAS exome AF: 0.638

Gnomad FIN exome AF: 0.265

Gnomad NFE exome AF: 0.175

Gnomad OTH exome AF: 0.231

GnomAD4 exome AF: 0.214 AC: 312320 AN: 1461814 Hom.: 39776 Cov.: 35 AF XY: 0.217 AC XY: 157648 AN XY: 727212

African (AFR) AF: 0.229 AC: 7661 AN: 33478

American (AMR) AF: 0.397 AC: 17738 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 4575 AN: 26134

East Asian (EAS) AF: 0.599 AC: 23786 AN: 39696

South Asian (SAS) AF: 0.360 AC: 31063 AN: 86248

European-Finnish (FIN) AF: 0.253 AC: 13519 AN: 53410

Middle Eastern (MID) AF: 0.156 AC: 898 AN: 5768

European-Non Finnish (NFE) AF: 0.179 AC: 199142 AN: 1111966

Other (OTH) AF: 0.231 AC: 13938 AN: 60390

GnomAD4 genome AF: 0.236 AC: 35870 AN: 152154 Hom.: 4965 Cov.: 33 AF XY: 0.245 AC XY: 18230 AN XY: 74380

African (AFR) AF: 0.229 AC: 9502 AN: 41504

American (AMR) AF: 0.335 AC: 5119 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 627 AN: 3472

East Asian (EAS) AF: 0.632 AC: 3270 AN: 5178

South Asian (SAS) AF: 0.364 AC: 1753 AN: 4820

European-Finnish (FIN) AF: 0.275 AC: 2911 AN: 10570

Middle Eastern (MID) AF: 0.120 AC: 35 AN: 292

European-Non Finnish (NFE) AF: 0.177 AC: 12051 AN: 67998

Other (OTH) AF: 0.212 AC: 447 AN: 2112

Alfa AF: 0.193 Hom.: 1571

Bravo AF: 0.238

Asia WGS AF: 0.446 AC: 1554 AN: 3478

EpiCase AF: 0.171

EpiControl AF: 0.167

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	not specified (2)
-	-	1	Inborn genetic diseases (1)
-	-	1	Intellectual disability, autosomal recessive 13 (1)
-	-	1	Intellectual Disability, Recessive (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	5.0
DANN	Benign	0.70
PhyloP100		0.24
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: rs12549048; hg19: chr8-141310644; COSMIC: COSV66900380;