4-183663736-GTTTTTTTT-GTTTTTTTTTTT

Variant names:

• chr4-183663736-G-GTTT
• rs70959134
• NM_021942.6:c.-21-94_-21-92dupTTT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_021942.6(TRAPPC11):​c.-21-94_-21-92dupTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00181 in 388,234 control chromosomes in the GnomAD database, including 9 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00053 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0023 (9 hom.)
• 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: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000528 (57/108022) while in subpopulation AFR AF = 0.00132 (39/29526). AF 95% confidence interval is 0.000993. There are 0 homozygotes in GnomAd4. There are 30 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 9 AR gene

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.-21-94_-21-92dupTTT		intron	N/A	NP_068761.4
	TRAPPC11	NM_199053.3		c.-21-94_-21-92dupTTT		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_-21-110insTTT		intron	N/A	ENSP00000335371.6	Q7Z392-1
	TRAPPC11	ENST00000357207.8	TSL:1	c.-21-111_-21-110insTTT		intron	N/A	ENSP00000349738.4	Q7Z392-3
	TRAPPC11	ENST00000505676.5	TSL:1	n.-21-111_-21-110insTTT		intron	N/A	ENSP00000422915.1	D6R9T9

Frequencies

GnomAD3 genomes AF: 0.000537 AC: 58 AN: 108030 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00132

Gnomad AMI AF: 0.00130

Gnomad AMR AF: 0.000378

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000291

Gnomad SAS AF: 0.000619

Gnomad FIN AF: 0.000213

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000175

Gnomad OTH AF: 0.000683

GnomAD4 exome AF: 0.00230 AC: 644 AN: 280212 Hom.: 9 AF XY: 0.00229 AC XY: 337 AN XY: 147192

African (AFR) AF: 0.00729 AC: 52 AN: 7130

American (AMR) AF: 0.00377 AC: 42 AN: 11150

Ashkenazi Jewish (ASJ) AF: 0.00122 AC: 10 AN: 8202

East Asian (EAS) AF: 0.00162 AC: 29 AN: 17876

South Asian (SAS) AF: 0.00358 AC: 97 AN: 27094

European-Finnish (FIN) AF: 0.00128 AC: 26 AN: 20358

Middle Eastern (MID) AF: 0.00173 AC: 2 AN: 1156

European-Non Finnish (NFE) AF: 0.00209 AC: 358 AN: 171362

Other (OTH) AF: 0.00176 AC: 28 AN: 15884

GnomAD4 genome AF: 0.000528 AC: 57 AN: 108022 Hom.: 0 Cov.: 0 AF XY: 0.000588 AC XY: 30 AN XY: 51058

African (AFR) AF: 0.00132 AC: 39 AN: 29526

American (AMR) AF: 0.000377 AC: 4 AN: 10600

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

East Asian (EAS) AF: 0.000292 AC: 1 AN: 3424

South Asian (SAS) AF: 0.000310 AC: 1 AN: 3228

European-Finnish (FIN) AF: 0.000213 AC: 1 AN: 4686

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 196

European-Non Finnish (NFE) AF: 0.000175 AC: 9 AN: 51290

Other (OTH) AF: 0.000681 AC: 1 AN: 1468

Alfa AF: 0.00 Hom.: 0

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;