14-39150383-TAAA-TAAAA

Variant names:

• chr14-39150383-T-TA
• rs150886646
• NM_001079537.2:c.446-3dupT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001079537.2(TRAPPC6B):​c.446-3dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0217 in 1,193,754 control chromosomes in the GnomAD database, including 5 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0013 (3 hom., cov: 31)
  • Exomes 𝑓: 0.025 (2 hom.)
• Consequence: TRAPPC6B NM_001079537.2 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0690
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 14-39150383-T-TA is Benign according to our data. Variant chr14-39150383-T-TA is described in ClinVar as Benign. ClinVar VariationId is 1987185.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00125 (184/146664) while in subpopulation EAS AF = 0.0283 (143/5048). AF 95% confidence interval is 0.0245. There are 3 homozygotes in GnomAd4. There are 109 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

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

Frequencies

GnomAD3 genomes AF: 0.00126 AC: 184 AN: 146602 Hom.: 3 Cov.: 31

Gnomad AFR AF: 0.000225

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000685

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0282

Gnomad SAS AF: 0.00171

Gnomad FIN AF: 0.000108

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000181

Gnomad OTH AF: 0.000505

GnomAD2 exomes AF: 0.0346 AC: 3238 AN: 93580 AF XY: 0.0340

Gnomad AFR exome AF: 0.0290

Gnomad AMR exome AF: 0.0565

Gnomad ASJ exome AF: 0.0470

Gnomad EAS exome AF: 0.0929

Gnomad FIN exome AF: 0.0162

Gnomad NFE exome AF: 0.0232

Gnomad OTH exome AF: 0.0356

GnomAD4 exome AF: 0.0246 AC: 25717 AN: 1047090 Hom.: 2 Cov.: 19 AF XY: 0.0239 AC XY: 12380 AN XY: 517888

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

African (AFR) AF: 0.0288 AC: 654 AN: 22744

American (AMR) AF: 0.0283 AC: 842 AN: 29720

Ashkenazi Jewish (ASJ) AF: 0.0268 AC: 447 AN: 16674

East Asian (EAS) AF: 0.0574 AC: 1498 AN: 26118

South Asian (SAS) AF: 0.0250 AC: 1395 AN: 55730

European-Finnish (FIN) AF: 0.0172 AC: 499 AN: 28932

Middle Eastern (MID) AF: 0.0177 AC: 77 AN: 4342

European-Non Finnish (NFE) AF: 0.0235 AC: 19267 AN: 820562

Other (OTH) AF: 0.0246 AC: 1038 AN: 42268

⚠️ 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 AF: 0.00125 AC: 184 AN: 146664 Hom.: 3 Cov.: 31 AF XY: 0.00153 AC XY: 109 AN XY: 71302

African (AFR) AF: 0.000224 AC: 9 AN: 40112

American (AMR) AF: 0.000685 AC: 10 AN: 14604

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

East Asian (EAS) AF: 0.0283 AC: 143 AN: 5048

South Asian (SAS) AF: 0.00171 AC: 8 AN: 4674

European-Finnish (FIN) AF: 0.000108 AC: 1 AN: 9294

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 280

European-Non Finnish (NFE) AF: 0.000181 AC: 12 AN: 66362

Other (OTH) AF: 0.000500 AC: 1 AN: 2000

Alfa AF: 0.0205 Hom.: 32

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.069
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: COSV57527755; COSMIC: COSV57527755;