14-39150383-TAAA-TA

Variant names:

• chr14-39150383-TAA-T
• rs150886646
• NM_001079537.2:c.446-4_446-3delTT

Variant summary

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

The NM_001079537.2(TRAPPC6B):​c.446-4_446-3delTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000103 in 1,136,244 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00010 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TRAPPC6B NM_001079537.2 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.23
• Publications: 1 publications found

Genes affected

TRAPPC6B (HGNC:23066): (trafficking protein particle complex subunit 6B) TRAPPC6B is a component of TRAPP complexes, which are tethering complexes involved in vesicle transport (Kummel et al., 2005 [PubMed 16025134]).[supplied by OMIM, Mar 2008]

TRAPPC6B Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with microcephaly, epilepsy, and brain atrophy

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Illumina, Ambry Genetics

ENSG00000285830 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001079537.2. 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
	TRAPPC6B	NM_001079537.2	MANE Select	c.446-4_446-3delTT		splice_region intron	N/A	NP_001073005.1	Q86SZ2-1
	TRAPPC6B	NM_177452.4		c.362-4_362-3delTT		splice_region intron	N/A	NP_803235.1	Q86SZ2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAPPC6B	ENST00000330149.10	TSL:1 MANE Select	c.446-4_446-3delTT		splice_region intron	N/A	ENSP00000330289.5	Q86SZ2-1
	TRAPPC6B	ENST00000347691.9	TSL:1	c.362-4_362-3delTT		splice_region intron	N/A	ENSP00000335171.6	Q86SZ2-2
	TRAPPC6B	ENST00000555269.5	TSL:1	n.*326-4_*326-3delTT		splice_region intron	N/A	ENSP00000452236.1	G3V4C3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 146682 Hom.: 0 Cov.: 31

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

GnomAD2 exomes AF: 0.000192 AC: 18 AN: 93580 AF XY: 0.000259

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000358

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000150

Gnomad NFE exome AF: 0.000167

Gnomad OTH exome AF: 0.000451

GnomAD4 exome AF: 0.000103 AC: 117 AN: 1136244 Hom.: 0 AF XY: 0.000115 AC XY: 65 AN XY: 563810

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

African (AFR) AF: 0.000161 AC: 4 AN: 24856

American (AMR) AF: 0.000252 AC: 8 AN: 31776

Ashkenazi Jewish (ASJ) AF: 0.0000533 AC: 1 AN: 18766

East Asian (EAS) AF: 0.00 AC: 0 AN: 29230

South Asian (SAS) AF: 0.0000968 AC: 6 AN: 61992

European-Finnish (FIN) AF: 0.0000628 AC: 2 AN: 31862

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4664

European-Non Finnish (NFE) AF: 0.000103 AC: 91 AN: 886814

Other (OTH) AF: 0.000108 AC: 5 AN: 46284

⚠️ 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 Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 146682 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 71272

African (AFR) AF: 0.00 AC: 0 AN: 40020

American (AMR) AF: 0.00 AC: 0 AN: 14610

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3396

East Asian (EAS) AF: 0.00 AC: 0 AN: 5066

South Asian (SAS) AF: 0.00 AC: 0 AN: 4690

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9320

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 306

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66398

Other (OTH) AF: 0.00 AC: 0 AN: 1982

Alfa AF: 0.000456 Hom.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs150886646; hg19: chr14-39619587; COSMIC: COSV57528404; COSMIC: COSV57528404;