4-183663736-GTTTTTTTT-GTTTTTTTTT

Variant names:

• chr4-183663736-G-GT
• rs70959134
• NM_021942.6:c.-21-92dupT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_021942.6(TRAPPC11):​c.-21-92dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 388,094 control chromosomes in the GnomAD database, including 5,062 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.29 (4405 hom., cov: 0)
  • Exomes 𝑓: 0.035 (657 hom.)
• Consequence: TRAPPC11 NM_021942.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.751
• Publications: 0 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: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), G2P, Myriad Women’s Health, 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 -10 ACMG points.

• BP6: Variant 4-183663736-G-GT is Benign according to our data. Variant chr4-183663736-G-GT is described in ClinVar as Benign. ClinVar VariationId is 1296244.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.354 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAPPC11	NM_021942.6	MANE Select	c.-21-92dupT		intron	N/A	NP_068761.4
	TRAPPC11	NM_199053.3		c.-21-92dupT		intron	N/A	NP_951008.1	Q7Z392-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAPPC11	ENST00000334690.11	TSL:1 MANE Select	c.-21-111_-21-110insT		intron	N/A	ENSP00000335371.6	Q7Z392-1
	TRAPPC11	ENST00000357207.8	TSL:1	c.-21-111_-21-110insT		intron	N/A	ENSP00000349738.4	Q7Z392-3
	TRAPPC11	ENST00000505676.5	TSL:1	n.-21-111_-21-110insT		intron	N/A	ENSP00000422915.1	D6R9T9

Frequencies

GnomAD3 genomes AF: 0.294 AC: 31731 AN: 108026 Hom.: 4407 Cov.: 0

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.295

GnomAD4 exome AF: 0.0351 AC: 9821 AN: 280076 Hom.: 657 AF XY: 0.0370 AC XY: 5440 AN XY: 147126

African (AFR) AF: 0.0674 AC: 479 AN: 7112

American (AMR) AF: 0.0654 AC: 729 AN: 11146

Ashkenazi Jewish (ASJ) AF: 0.0264 AC: 216 AN: 8196

East Asian (EAS) AF: 0.0270 AC: 483 AN: 17880

South Asian (SAS) AF: 0.0648 AC: 1754 AN: 27070

European-Finnish (FIN) AF: 0.0186 AC: 379 AN: 20352

Middle Eastern (MID) AF: 0.0312 AC: 36 AN: 1154

European-Non Finnish (NFE) AF: 0.0309 AC: 5299 AN: 171290

Other (OTH) AF: 0.0281 AC: 446 AN: 15876

GnomAD4 genome AF: 0.294 AC: 31733 AN: 108018 Hom.: 4405 Cov.: 0 AF XY: 0.287 AC XY: 14651 AN XY: 51068

African (AFR) AF: 0.359 AC: 10609 AN: 29530

American (AMR) AF: 0.291 AC: 3089 AN: 10598

Ashkenazi Jewish (ASJ) AF: 0.394 AC: 1117 AN: 2834

East Asian (EAS) AF: 0.187 AC: 640 AN: 3424

South Asian (SAS) AF: 0.219 AC: 706 AN: 3230

European-Finnish (FIN) AF: 0.128 AC: 598 AN: 4688

Middle Eastern (MID) AF: 0.294 AC: 57 AN: 194

European-Non Finnish (NFE) AF: 0.276 AC: 14131 AN: 51282

Other (OTH) AF: 0.294 AC: 431 AN: 1464

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.75
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: rs70959134; hg19: chr4-184584889; COSMIC: COSV58215110; COSMIC: COSV58215110;