chr4-183663736-G-GTTTTTTTT

Variant names:

• chr4-183663736-G-GTTTTTTTT
• rs70959134
• NM_021942.6:c.-21-99_-21-92dupTTTTTTTT

Variant summary

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

The NM_021942.6(TRAPPC11):​c.-21-99_-21-92dupTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000714 in 280,282 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0000071 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: TRAPPC11 NM_021942.6 intron
• Clinical Significance: Not reported in ClinVar
• 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: 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.-21-99_-21-92dupTTTTTTTT		intron	N/A	NP_068761.4
	TRAPPC11	NM_199053.3		c.-21-99_-21-92dupTTTTTTTT		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_-21-110insTTTTTTTT		intron	N/A	ENSP00000335371.6	Q7Z392-1
	TRAPPC11	ENST00000357207.8	TSL:1	c.-21-111_-21-110insTTTTTTTT		intron	N/A	ENSP00000349738.4	Q7Z392-3
	TRAPPC11	ENST00000505676.5	TSL:1	n.-21-111_-21-110insTTTTTTTT		intron	N/A	ENSP00000422915.1	D6R9T9

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 108062 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000714 AC: 2 AN: 280282 Hom.: 1 AF XY: 0.00 AC XY: 0 AN XY: 147232

African (AFR) AF: 0.00 AC: 0 AN: 7138

American (AMR) AF: 0.00 AC: 0 AN: 11160

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8202

East Asian (EAS) AF: 0.00 AC: 0 AN: 17882

South Asian (SAS) AF: 0.00 AC: 0 AN: 27102

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20360

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1156

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 171396

Other (OTH) AF: 0.000126 AC: 2 AN: 15886

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 108062 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 51066

African (AFR) AF: 0.00 AC: 0 AN: 29512

American (AMR) AF: 0.00 AC: 0 AN: 10592

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2834

East Asian (EAS) AF: 0.00 AC: 0 AN: 3444

South Asian (SAS) AF: 0.00 AC: 0 AN: 3232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4686

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 216

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 51308

Other (OTH) AF: 0.00 AC: 0 AN: 1466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.75

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;