NM_001079537.2:c.446-3delT

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001079537.2(TRAPPC6B):​c.446-3delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 1,141,986 control chromosomes in the GnomAD database, including 2,040 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.043 (170 hom., cov: 31)
  • Exomes 𝑓: 0.12 (1870 hom.)
• Consequence: TRAPPC6B NM_001079537.2 splice_region, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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 -16 ACMG points.

• BP6: Variant 14-39150383-TA-T is Benign according to our data. Variant chr14-39150383-TA-T is described in ClinVar as Benign. ClinVar VariationId is 1598887.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0683 is higher than 0.05.

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

Frequencies

GnomAD3 genomes AF: 0.0435 AC: 6368 AN: 146486 Hom.: 170 Cov.: 31

Gnomad AFR AF: 0.0124

Gnomad AMI AF: 0.0179

Gnomad AMR AF: 0.0367

Gnomad ASJ AF: 0.0109

Gnomad EAS AF: 0.00336

Gnomad SAS AF: 0.0252

Gnomad FIN AF: 0.0465

Gnomad MID AF: 0.00987

Gnomad NFE AF: 0.0700

Gnomad OTH AF: 0.0374

GnomAD2 exomes AF: 0.158 AC: 14815 AN: 93580 AF XY: 0.161

Gnomad AFR exome AF: 0.0894

Gnomad AMR exome AF: 0.163

Gnomad ASJ exome AF: 0.120

Gnomad EAS exome AF: 0.0909

Gnomad FIN exome AF: 0.127

Gnomad NFE exome AF: 0.183

Gnomad OTH exome AF: 0.173

GnomAD4 exome AF: 0.115 AC: 114568 AN: 995442 Hom.: 1870 Cov.: 19 AF XY: 0.115 AC XY: 56277 AN XY: 490536

African (AFR) AF: 0.0540 AC: 1170 AN: 21666

American (AMR) AF: 0.0876 AC: 2427 AN: 27698

Ashkenazi Jewish (ASJ) AF: 0.0653 AC: 973 AN: 14898

East Asian (EAS) AF: 0.0432 AC: 1032 AN: 23880

South Asian (SAS) AF: 0.0865 AC: 4398 AN: 50824

European-Finnish (FIN) AF: 0.102 AC: 2720 AN: 26586

Middle Eastern (MID) AF: 0.0497 AC: 204 AN: 4106

European-Non Finnish (NFE) AF: 0.124 AC: 97242 AN: 786014

Other (OTH) AF: 0.111 AC: 4402 AN: 39770

GnomAD4 genome AF: 0.0434 AC: 6365 AN: 146544 Hom.: 170 Cov.: 31 AF XY: 0.0404 AC XY: 2876 AN XY: 71232

African (AFR) AF: 0.0123 AC: 495 AN: 40082

American (AMR) AF: 0.0366 AC: 535 AN: 14600

Ashkenazi Jewish (ASJ) AF: 0.0109 AC: 37 AN: 3392

East Asian (EAS) AF: 0.00336 AC: 17 AN: 5052

South Asian (SAS) AF: 0.0253 AC: 118 AN: 4672

European-Finnish (FIN) AF: 0.0465 AC: 430 AN: 9250

Middle Eastern (MID) AF: 0.0108 AC: 3 AN: 278

European-Non Finnish (NFE) AF: 0.0700 AC: 4641 AN: 66324

Other (OTH) AF: 0.0365 AC: 73 AN: 2000

Alfa AF: 0.0788 Hom.: 32

Bravo AF: 0.0399

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

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

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: COSV57527453; COSMIC: COSV57527453;