14-39150383-TAAA-TAAAAAA

Variant names:

• chr14-39150383-T-TAAA
• rs150886646
• NM_001079537.2:c.446-5_446-3dupTTT

Variant summary

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

The NM_001079537.2(TRAPPC6B):​c.446-5_446-3dupTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000264 in 1,138,340 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: 31)
  • Exomes 𝑓: 0.0000026 (0 hom.)
• Consequence: TRAPPC6B NM_001079537.2 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0690
• Publications: 0 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 2 ACMG points.

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

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.446-5_446-3dupTTT		splice_region intron	N/A	NP_001073005.1	Q86SZ2-1
	TRAPPC6B	NM_177452.4		c.362-5_362-3dupTTT		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.446-5_446-3dupTTT		splice_region intron	N/A	ENSP00000330289.5	Q86SZ2-1
	TRAPPC6B	ENST00000347691.9	TSL:1	c.362-5_362-3dupTTT		splice_region intron	N/A	ENSP00000335171.6	Q86SZ2-2
	TRAPPC6B	ENST00000555269.5	TSL:1	n.*326-5_*326-3dupTTT		splice_region intron	N/A	ENSP00000452236.1	G3V4C3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000264 AC: 3 AN: 1138340 Hom.: 0 Cov.: 19 AF XY: 0.00000354 AC XY: 2 AN XY: 564804

⚠️ 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: 24906

American (AMR) AF: 0.00 AC: 0 AN: 31856

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18804

East Asian (EAS) AF: 0.00 AC: 0 AN: 29266

South Asian (SAS) AF: 0.00 AC: 0 AN: 62082

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31898

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4672

European-Non Finnish (NFE) AF: 0.00000338 AC: 3 AN: 888512

Other (OTH) AF: 0.00 AC: 0 AN: 46344

⚠️ 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.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.069

Splicing

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

Other links and lift over

dbSNP: rs150886646; hg19: chr14-39619587;