4-183663736-GTTTTTTTT-GTTTTTTTTTTTT

Variant names:

• chr4-183663736-G-GTTTT
• rs70959134
• NM_021942.6:c.-21-95_-21-92dupTTTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_021942.6(TRAPPC11):​c.-21-95_-21-92dupTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000479 in 388,274 control chromosomes in the GnomAD database, including 4 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00061 (4 hom.)
• Consequence: TRAPPC11 NM_021942.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.751

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.000614 (172/280254) while in subpopulation AFR AF= 0.00196 (14/7134). AF 95% confidence interval is 0.00119. There are 4 homozygotes in gnomad4_exome. There are 103 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAPPC11	NM_021942.6	c.-21-95_-21-92dupTTTT		intron_variant	Intron 1 of 29	ENST00000334690.11	NP_068761.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAPPC11	ENST00000334690.11	c.-21-111_-21-110insTTTT		intron_variant	Intron 1 of 29	1	NM_021942.6	ENSP00000335371.6
TRAPPC11	ENST00000357207.8	c.-21-111_-21-110insTTTT		intron_variant	Intron 1 of 30	1		ENSP00000349738.4
TRAPPC11	ENST00000505676.5	n.-21-111_-21-110insTTTT		intron_variant	Intron 1 of 18	1		ENSP00000422915.1
TRAPPC11	ENST00000504526.1	n.126-111_126-110insTTTT		intron_variant	Intron 1 of 2	4

Frequencies

GnomAD3 genomes AF: 0.000130 AC: 14 AN: 108028 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000271

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000944

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: 0.0000975

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000614 AC: 172 AN: 280254 Hom.: 4 AF XY: 0.000700 AC XY: 103 AN XY: 147218

Gnomad4 AFR exome AF: 0.00196

Gnomad4 AMR exome AF: 0.000807

Gnomad4 ASJ exome AF: 0.000488

Gnomad4 EAS exome AF: 0.000280

Gnomad4 SAS exome AF: 0.00140

Gnomad4 FIN exome AF: 0.000246

Gnomad4 NFE exome AF: 0.000525

Gnomad4 OTH exome AF: 0.000441

GnomAD4 genome AF: 0.000130 AC: 14 AN: 108020 Hom.: 0 Cov.: 0 AF XY: 0.000118 AC XY: 6 AN XY: 51062

Gnomad4 AFR AF: 0.000271

Gnomad4 AMR AF: 0.0000943

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000975

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs70959134; hg19: chr4-184584889;