rs4862234

Variant names:

• chr4-183693721-C-T
• rs4862234
• NM_021942.6:c.2370C>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_021942.6(TRAPPC11):​c.2370C>T​(p.Thr790Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 1,613,170 control chromosomes in the GnomAD database, including 44,446 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (4767 hom., cov: 32)
  • Exomes 𝑓: 0.23 (39679 hom.)
• Consequence: TRAPPC11 NM_021942.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -2.74
• Publications: 12 publications found

Genes affected

TRAPPC11 (HGNC:25751): (trafficking protein particle complex subunit 11) The protein encoded by this gene is a subunit of the TRAPP (transport protein particle) tethering complex, which functions in intracellular vesicle trafficking. This subunit is involved in early stage endoplasmic reticulum-to-Golgi vesicle transport. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jan 2013]

TRAPPC11 Gene-Disease associations (from GenCC):

• autosomal recessive limb-girdle muscular dystrophy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• autosomal recessive limb-girdle muscular dystrophy type R18

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Myriad Women’s Health, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, G2P, Orphanet
• intellectual disability-hyperkinetic movement-truncal ataxia syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• triple-A syndrome

  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 (BayesDel_noAF=-0.29).
• BP6: Variant 4-183693721-C-T is Benign according to our data. Variant chr4-183693721-C-T is described in ClinVar as Benign. ClinVar VariationId is 261446.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.74 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021942.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAPPC11	NM_021942.6	MANE Select	c.2370C>T	p.Thr790Thr	synonymous	Exon 21 of 30	NP_068761.4
	TRAPPC11	NM_199053.3		c.2370C>T	p.Thr790Thr	synonymous	Exon 21 of 31	NP_951008.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAPPC11	ENST00000334690.11	TSL:1 MANE Select	c.2370C>T	p.Thr790Thr	synonymous	Exon 21 of 30	ENSP00000335371.6
	TRAPPC11	ENST00000357207.8	TSL:1	c.2370C>T	p.Thr790Thr	synonymous	Exon 21 of 31	ENSP00000349738.4
	TRAPPC11	ENST00000512476.1	TSL:1	c.1188C>T	p.Thr396Thr	synonymous	Exon 10 of 19	ENSP00000421004.1

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37266 AN: 151906 Hom.: 4761 Cov.: 32

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.198

GnomAD2 exomes AF: 0.217 AC: 54442 AN: 250474 AF XY: 0.213

Gnomad AFR exome AF: 0.318

Gnomad AMR exome AF: 0.192

Gnomad ASJ exome AF: 0.145

Gnomad EAS exome AF: 0.170

Gnomad FIN exome AF: 0.279

Gnomad NFE exome AF: 0.230

Gnomad OTH exome AF: 0.202

GnomAD4 exome AF: 0.229 AC: 335051 AN: 1461146 Hom.: 39679 Cov.: 34 AF XY: 0.226 AC XY: 164553 AN XY: 726862

African (AFR) AF: 0.310 AC: 10369 AN: 33432

American (AMR) AF: 0.195 AC: 8705 AN: 44570

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 3775 AN: 26098

East Asian (EAS) AF: 0.162 AC: 6433 AN: 39686

South Asian (SAS) AF: 0.158 AC: 13560 AN: 86054

European-Finnish (FIN) AF: 0.278 AC: 14852 AN: 53396

Middle Eastern (MID) AF: 0.158 AC: 912 AN: 5764

European-Non Finnish (NFE) AF: 0.237 AC: 263569 AN: 1111780

Other (OTH) AF: 0.213 AC: 12876 AN: 60366

GnomAD4 genome AF: 0.245 AC: 37319 AN: 152024 Hom.: 4767 Cov.: 32 AF XY: 0.243 AC XY: 18057 AN XY: 74292

African (AFR) AF: 0.310 AC: 12857 AN: 41440

American (AMR) AF: 0.195 AC: 2982 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 489 AN: 3468

East Asian (EAS) AF: 0.171 AC: 885 AN: 5172

South Asian (SAS) AF: 0.163 AC: 786 AN: 4822

European-Finnish (FIN) AF: 0.282 AC: 2967 AN: 10538

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.231 AC: 15712 AN: 67984

Other (OTH) AF: 0.196 AC: 415 AN: 2112

Alfa AF: 0.230 Hom.: 7501

Bravo AF: 0.243

Asia WGS AF: 0.160 AC: 555 AN: 3478

EpiCase AF: 0.219

EpiControl AF: 0.218

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	3	not specified (3)
-	-	2	Autosomal recessive limb-girdle muscular dystrophy type R18 (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	0.24
DANN	Benign	0.64
PhyloP100		-2.7
Mutation Taster		=94/6	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs4862234; hg19: chr4-184614874; COSMIC: COSV58215124;