NM_021942.6:c.-21-96_-21-92delTTTTT

Variant names:

• chr4-183663736-GTTTTT-G
• rs70959134
• NM_021942.6:c.-21-96_-21-92delTTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_021942.6(TRAPPC11):​c.-21-96_-21-92delTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000114 in 280,010 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: TRAPPC11 NM_021942.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.972
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.-21-96_-21-92delTTTTT		intron	N/A	NP_068761.4
	TRAPPC11	NM_199053.3		c.-21-96_-21-92delTTTTT		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.-21-110_-21-106delTTTTT		intron	N/A	ENSP00000335371.6	Q7Z392-1
	TRAPPC11	ENST00000357207.8	TSL:1	c.-21-110_-21-106delTTTTT		intron	N/A	ENSP00000349738.4	Q7Z392-3
	TRAPPC11	ENST00000505676.5	TSL:1	n.-21-110_-21-106delTTTTT		intron	N/A	ENSP00000422915.1	D6R9T9

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.000114 AC: 32 AN: 280010 Hom.: 0 AF XY: 0.000116 AC XY: 17 AN XY: 147098

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 7132

American (AMR) AF: 0.000269 AC: 3 AN: 11142

Ashkenazi Jewish (ASJ) AF: 0.000122 AC: 1 AN: 8200

East Asian (EAS) AF: 0.0000560 AC: 1 AN: 17868

South Asian (SAS) AF: 0.000111 AC: 3 AN: 27052

European-Finnish (FIN) AF: 0.0000983 AC: 2 AN: 20348

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1154

European-Non Finnish (NFE) AF: 0.000117 AC: 20 AN: 171250

Other (OTH) AF: 0.000126 AC: 2 AN: 15864

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.97

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;