4-183675156-CTT-CT

Variant names:

• chr4-183675156-CT-C
• rs140871779
• NM_021942.6:c.661-3delT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_021942.6(TRAPPC11):​c.661-3delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 1,474,534 control chromosomes in the GnomAD database, including 9,177 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.094 (801 hom., cov: 31)
  • Exomes 𝑓: 0.11 (8376 hom.)
• Consequence: TRAPPC11 NM_021942.6 splice_region, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0740
• Publications: 5 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 -16 ACMG points.

• BP6: Variant 4-183675156-CT-C is Benign according to our data. Variant chr4-183675156-CT-C is described in ClinVar as Benign. ClinVar VariationId is 261454.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.123 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.661-3delT		splice_region intron	N/A	NP_068761.4
	TRAPPC11	NM_199053.3		c.661-3delT		splice_region intron	N/A	NP_951008.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAPPC11	ENST00000334690.11	TSL:1 MANE Select	c.661-7delT		splice_region intron	N/A	ENSP00000335371.6
	TRAPPC11	ENST00000357207.8	TSL:1	c.661-7delT		splice_region intron	N/A	ENSP00000349738.4
	TRAPPC11	ENST00000505676.5	TSL:1	n.163-5051delT		intron	N/A	ENSP00000422915.1

Frequencies

GnomAD3 genomes AF: 0.0936 AC: 14205 AN: 151776 Hom.: 797 Cov.: 31

Gnomad AFR AF: 0.0231

Gnomad AMI AF: 0.0822

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.0934

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.0883

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.0920

GnomAD2 exomes AF: 0.116 AC: 23224 AN: 200328 AF XY: 0.114

Gnomad AFR exome AF: 0.0234

Gnomad AMR exome AF: 0.151

Gnomad ASJ exome AF: 0.0972

Gnomad EAS exome AF: 0.129

Gnomad FIN exome AF: 0.184

Gnomad NFE exome AF: 0.114

Gnomad OTH exome AF: 0.114

GnomAD4 exome AF: 0.108 AC: 143326 AN: 1322640 Hom.: 8376 Cov.: 19 AF XY: 0.108 AC XY: 70950 AN XY: 656782

African (AFR) AF: 0.0201 AC: 583 AN: 29018

American (AMR) AF: 0.148 AC: 4500 AN: 30462

Ashkenazi Jewish (ASJ) AF: 0.0959 AC: 2174 AN: 22664

East Asian (EAS) AF: 0.101 AC: 3678 AN: 36564

South Asian (SAS) AF: 0.0815 AC: 5148 AN: 63204

European-Finnish (FIN) AF: 0.180 AC: 8894 AN: 49352

Middle Eastern (MID) AF: 0.116 AC: 503 AN: 4318

European-Non Finnish (NFE) AF: 0.109 AC: 112267 AN: 1033122

Other (OTH) AF: 0.103 AC: 5579 AN: 53936

GnomAD4 genome AF: 0.0936 AC: 14224 AN: 151894 Hom.: 801 Cov.: 31 AF XY: 0.0970 AC XY: 7199 AN XY: 74220

African (AFR) AF: 0.0230 AC: 956 AN: 41502

American (AMR) AF: 0.127 AC: 1945 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.0934 AC: 324 AN: 3468

East Asian (EAS) AF: 0.123 AC: 638 AN: 5176

South Asian (SAS) AF: 0.0888 AC: 428 AN: 4820

European-Finnish (FIN) AF: 0.186 AC: 1939 AN: 10444

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.113 AC: 7682 AN: 67910

Other (OTH) AF: 0.0958 AC: 202 AN: 2108

Alfa AF: 0.0576 Hom.: 92

Bravo AF: 0.0873

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Autosomal recessive limb-girdle muscular dystrophy type R18 (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.074
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: rs140871779; hg19: chr4-184596309; COSMIC: COSV58216126; COSMIC: COSV58216126;