Genetic Variant NM_001079537.2:c.352-17A>G (chr14-39151856-T-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS1

The NM_001079537.2(TRAPPC6B):c.352-17A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0003 in 1,518,150 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

TRAPPC6B
NM_001079537.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.312

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: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 14-39151856-T-C is Benign according to our data. Variant chr14-39151856-T-C is described in ClinVar as Benign. ClinVar VariationId is 1989714.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00154 (234/151900) while in subpopulation AFR AF = 0.00535 (221/41280). AF 95% confidence interval is 0.00477. There are 0 homozygotes in GnomAd4. There are 120 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

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.352-17A>G		intron	N/A	NP_001073005.1	Q86SZ2-1
	TRAPPC6B	NM_177452.4		c.268-17A>G		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.352-17A>G	intron	N/A	ENSP00000330289.5	Q86SZ2-1
TRAPPC6B	ENST00000347691.9	TSL:1	c.268-17A>G	intron	N/A	ENSP00000335171.6	Q86SZ2-2
TRAPPC6B	ENST00000555269.5	TSL:1	n.*232-17A>G	intron	N/A	ENSP00000452236.1	G3V4C3

Frequencies

GnomAD3 genomes

AF:

0.00153

AC:

232

AN:

151780

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00532

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000328

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00192

GnomAD2 exomes

AF:

0.000362

AC:

AN:

221242

AF XY:

0.000307

show subpopulations

Gnomad AFR exome

AF:

0.00485

Gnomad AMR exome

AF:

0.0000392

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000953

Gnomad OTH exome

AF:

0.000191

GnomAD4 exome

AF:

0.000162

AC:

222

AN:

1366250

Hom.:

Cov.:

AF XY:

0.000139

AC XY:

AN XY:

683340

show subpopulations

African (AFR)

AF:

0.00529

AC:

151

AN:

28532

American (AMR)

AF:

0.000196

AC:

AN:

35626

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24336

East Asian (EAS)

AF:

0.00

AC:

AN:

38756

South Asian (SAS)

AF:

0.000165

AC:

AN:

78728

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53006

Middle Eastern (MID)

AF:

0.000365

AC:

AN:

5480

European-Non Finnish (NFE)

AF:

0.0000211

AC:

AN:

1045050

Other (OTH)

AF:

0.000476

AC:

AN:

56736

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

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

AF:

0.00154

AC:

234

AN:

151900

Hom.:

Cov.:

AF XY:

0.00162

AC XY:

120

AN XY:

74282

show subpopulations

African (AFR)

AF:

0.00535

AC:

221

AN:

41280

American (AMR)

AF:

0.000328

AC:

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000415

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10588

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

67980

Other (OTH)

AF:

0.00190

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000692

Hom.:

Bravo

AF:

0.00181

ClinVar

ClinVar submissions

Significance: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

-0.81

CADD

Benign

1.8

(source)

DANN

Benign

0.70

PhyloP100

-0.31

Mutation Taster

=100/0

polymorphism

(source)

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

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over