dbSNP rs777012363: TRAPPC6B:c.351+7A>C (chr14-39154204-T-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_001079537.2(TRAPPC6B):c.351+7A>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000347 in 1,441,624 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

TRAPPC6B
NM_001079537.2 splice_region, intron

Scores

Splicing: ADA: 0.002166

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.25

Publications

0 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 14-39154204-T-G is Benign according to our data. Variant chr14-39154204-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1940078.Status of the report is criteria_provided_single_submitter, 1 stars.

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.351+7A>C		splice_region intron	N/A	NP_001073005.1	Q86SZ2-1
	TRAPPC6B	NM_177452.4		c.268-2365A>C		intron	N/A	NP_803235.1	Q86SZ2-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TRAPPC6B	ENST00000330149.10	TSL:1 MANE Select	c.351+7A>C	splice_region intron	N/A	ENSP00000330289.5	Q86SZ2-1
TRAPPC6B	ENST00000347691.9	TSL:1	c.268-2365A>C	intron	N/A	ENSP00000335171.6	Q86SZ2-2
TRAPPC6B	ENST00000555269.5	TSL:1	n.*231+7A>C	splice_region intron	N/A	ENSP00000452236.1	G3V4C3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000122

AC:

AN:

245510

AF XY:

0.00000750

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000887

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000347

AC:

AN:

1441624

Hom.:

Cov.:

AF XY:

0.00000278

AC XY:

AN XY:

718218

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32936

American (AMR)

AF:

0.000113

AC:

AN:

44092

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25762

East Asian (EAS)

AF:

0.00

AC:

AN:

39580

South Asian (SAS)

AF:

0.00

AC:

AN:

85520

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53270

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5732

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1095036

Other (OTH)

AF:

0.00

AC:

AN:

59696

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

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.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.70

PhyloP100

1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0022

dbscSNV1_RF

Benign

0.0040

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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