14-39151732-C-T

Variant names:

• chr14-39151732-C-T
• rs8003807
• NM_001079537.2:c.445+14G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001079537.2(TRAPPC6B):​c.445+14G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.927 in 1,541,016 control chromosomes in the GnomAD database, including 662,790 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.93 (65299 hom., cov: 30)
  • Exomes 𝑓: 0.93 (597491 hom.)
• Consequence: TRAPPC6B NM_001079537.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0640
• Publications: 10 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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 14-39151732-C-T is Benign according to our data. Variant chr14-39151732-C-T is described in ClinVar as Benign. ClinVar VariationId is 1342265.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.931 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.445+14G>A		intron	N/A	NP_001073005.1	Q86SZ2-1
	TRAPPC6B	NM_177452.4		c.361+14G>A		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.445+14G>A		intron	N/A	ENSP00000330289.5	Q86SZ2-1
	TRAPPC6B	ENST00000347691.9	TSL:1	c.361+14G>A		intron	N/A	ENSP00000335171.6	Q86SZ2-2
	TRAPPC6B	ENST00000555269.5	TSL:1	n.*325+14G>A		intron	N/A	ENSP00000452236.1	G3V4C3

Frequencies

GnomAD3 genomes AF: 0.927 AC: 140672 AN: 151816 Hom.: 65265 Cov.: 30

Gnomad AFR AF: 0.934

Gnomad AMI AF: 0.968

Gnomad AMR AF: 0.874

Gnomad ASJ AF: 0.920

Gnomad EAS AF: 0.951

Gnomad SAS AF: 0.848

Gnomad FIN AF: 0.931

Gnomad MID AF: 0.886

Gnomad NFE AF: 0.937

Gnomad OTH AF: 0.921

GnomAD2 exomes AF: 0.918 AC: 186771 AN: 203528 AF XY: 0.916

Gnomad AFR exome AF: 0.938

Gnomad AMR exome AF: 0.850

Gnomad ASJ exome AF: 0.921

Gnomad EAS exome AF: 0.954

Gnomad FIN exome AF: 0.927

Gnomad NFE exome AF: 0.939

Gnomad OTH exome AF: 0.918

GnomAD4 exome AF: 0.927 AC: 1287743 AN: 1389084 Hom.: 597491 Cov.: 22 AF XY: 0.926 AC XY: 640258 AN XY: 691704

African (AFR) AF: 0.931 AC: 27529 AN: 29582

American (AMR) AF: 0.852 AC: 25567 AN: 30010

Ashkenazi Jewish (ASJ) AF: 0.918 AC: 21774 AN: 23714

East Asian (EAS) AF: 0.968 AC: 36720 AN: 37926

South Asian (SAS) AF: 0.841 AC: 64201 AN: 76326

European-Finnish (FIN) AF: 0.924 AC: 48597 AN: 52590

Middle Eastern (MID) AF: 0.901 AC: 4952 AN: 5498

European-Non Finnish (NFE) AF: 0.934 AC: 1005614 AN: 1076138

Other (OTH) AF: 0.921 AC: 52789 AN: 57300

GnomAD4 genome AF: 0.926 AC: 140761 AN: 151932 Hom.: 65299 Cov.: 30 AF XY: 0.923 AC XY: 68536 AN XY: 74266

African (AFR) AF: 0.934 AC: 38734 AN: 41462

American (AMR) AF: 0.873 AC: 13307 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.920 AC: 3193 AN: 3472

East Asian (EAS) AF: 0.952 AC: 4932 AN: 5182

South Asian (SAS) AF: 0.848 AC: 4087 AN: 4822

European-Finnish (FIN) AF: 0.931 AC: 9746 AN: 10466

Middle Eastern (MID) AF: 0.874 AC: 257 AN: 294

European-Non Finnish (NFE) AF: 0.937 AC: 63694 AN: 67980

Other (OTH) AF: 0.916 AC: 1928 AN: 2104

Alfa AF: 0.927 Hom.: 11264

Bravo AF: 0.924

Asia WGS AF: 0.877 AC: 3039 AN: 3462

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Neurodevelopmental disorder with microcephaly, epilepsy, and brain atrophy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.9
DANN	Benign	0.51
PhyloP100		-0.064
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs8003807; hg19: chr14-39620936;