4-183663736-GTTTTTTTT-GTTTTTTTTTT

Variant names:

• chr4-183663736-G-GTT
• rs70959134
• NM_021942.6:c.-21-93_-21-92dupTT

Variant summary

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

The NM_021942.6(TRAPPC11):​c.-21-93_-21-92dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0151 in 388,146 control chromosomes in the GnomAD database, including 284 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.033 (219 hom., cov: 0)
  • Exomes 𝑓: 0.0080 (65 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-GTT is Benign according to our data. Variant chr4-183663736-G-GTT is described in ClinVar as Benign. ClinVar VariationId is 1241290.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.107 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.-21-93_-21-92dupTT		intron	N/A	NP_068761.4
	TRAPPC11	NM_199053.3		c.-21-93_-21-92dupTT		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_-21-110insTT		intron	N/A	ENSP00000335371.6	Q7Z392-1
	TRAPPC11	ENST00000357207.8	TSL:1	c.-21-111_-21-110insTT		intron	N/A	ENSP00000349738.4	Q7Z392-3
	TRAPPC11	ENST00000505676.5	TSL:1	n.-21-111_-21-110insTT		intron	N/A	ENSP00000422915.1	D6R9T9

Frequencies

GnomAD3 genomes AF: 0.0333 AC: 3601 AN: 108020 Hom.: 219 Cov.: 0

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.00518

Gnomad AMR AF: 0.0136

Gnomad ASJ AF: 0.00177

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.00278

Gnomad FIN AF: 0.000640

Gnomad MID AF: 0.0139

Gnomad NFE AF: 0.00275

Gnomad OTH AF: 0.0219

GnomAD4 exome AF: 0.00800 AC: 2241 AN: 280132 Hom.: 65 AF XY: 0.00810 AC XY: 1192 AN XY: 147166

African (AFR) AF: 0.0264 AC: 188 AN: 7122

American (AMR) AF: 0.0152 AC: 169 AN: 11154

Ashkenazi Jewish (ASJ) AF: 0.00744 AC: 61 AN: 8196

East Asian (EAS) AF: 0.00532 AC: 95 AN: 17868

South Asian (SAS) AF: 0.0132 AC: 357 AN: 27086

European-Finnish (FIN) AF: 0.00413 AC: 84 AN: 20358

Middle Eastern (MID) AF: 0.00693 AC: 8 AN: 1154

European-Non Finnish (NFE) AF: 0.00687 AC: 1177 AN: 171318

Other (OTH) AF: 0.00642 AC: 102 AN: 15876

GnomAD4 genome AF: 0.0334 AC: 3606 AN: 108014 Hom.: 219 Cov.: 0 AF XY: 0.0318 AC XY: 1625 AN XY: 51054

African (AFR) AF: 0.110 AC: 3262 AN: 29524

American (AMR) AF: 0.0136 AC: 144 AN: 10596

Ashkenazi Jewish (ASJ) AF: 0.00177 AC: 5 AN: 2832

East Asian (EAS) AF: 0.00117 AC: 4 AN: 3424

South Asian (SAS) AF: 0.00248 AC: 8 AN: 3228

European-Finnish (FIN) AF: 0.000640 AC: 3 AN: 4686

Middle Eastern (MID) AF: 0.0153 AC: 3 AN: 196

European-Non Finnish (NFE) AF: 0.00275 AC: 141 AN: 51288

Other (OTH) AF: 0.0218 AC: 32 AN: 1468

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

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs70959134; hg19: chr4-184584889;