Genetic Variant TRAPPC6B:p.Leu158Leu (chr14-39150353-C-T) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7

The NM_001079537.2(TRAPPC6B):c.474G>A(p.Leu158Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000447 in 1,432,134 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L158L) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000045 ( 0 hom. )

Consequence

TRAPPC6B
NM_001079537.2 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.733

Publications

1 publications found

Variant links:

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

TRAPPC6B links:

ENSG00000285830 (HGNC:):

ENSG00000285830 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP7

Synonymous conserved (PhyloP=-0.733 with no splicing effect.

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.474G>A	p.Leu158Leu	synonymous	Exon 6 of 6	NP_001073005.1	Q86SZ2-1
	TRAPPC6B	NM_177452.4		c.390G>A	p.Leu130Leu	synonymous	Exon 5 of 5	NP_803235.1	Q86SZ2-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRAPPC6B	ENST00000330149.10	TSL:1 MANE Select	c.474G>A	p.Leu158Leu	synonymous	Exon 6 of 6	ENSP00000330289.5	Q86SZ2-1
TRAPPC6B	ENST00000347691.9	TSL:1	c.390G>A	p.Leu130Leu	synonymous	Exon 5 of 5	ENSP00000335171.6	Q86SZ2-2
TRAPPC6B	ENST00000555269.5	TSL:1	n.*354G>A		non_coding_transcript_exon	Exon 6 of 6	ENSP00000452236.1	G3V4C3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000134

AC:

AN:

224036

AF XY:

0.0000165

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000283

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000447

AC:

AN:

1432134

Hom.:

Cov.:

AF XY:

0.0000449

AC XY:

AN XY:

712108

show subpopulations

African (AFR)

AF:

0.0000310

AC:

AN:

32240

American (AMR)

AF:

0.00

AC:

AN:

40436

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25536

East Asian (EAS)

AF:

0.00

AC:

AN:

39430

South Asian (SAS)

AF:

0.00

AC:

AN:

80886

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45088

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5708

European-Non Finnish (NFE)

AF:

0.0000553

AC:

AN:

1103312

Other (OTH)

AF:

0.0000336

AC:

AN:

59498

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.434

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Benign

0.72

PhyloP100

-0.73

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over