Variant 19-45164934-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_001270891.2(TRAPPC6A):c.189G>A(p.Leu63=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000665 in 1,614,160 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0036 ( 5 hom., cov: 33)

Exomes 𝑓: 0.00036 ( 4 hom. )

Consequence

TRAPPC6A
NM_001270891.2 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.551

Variant links:

Genes affected

TRAPPC6A (HGNC:23069): (trafficking protein particle complex subunit 6A) This gene encodes a component of the trafficking protein particle complex, which tethers transport vesicles to the cis-Golgi membrane. Loss of expression of the related gene in mouse affects coat and eye pigmentation, suggesting that the encoded protein may be involved in melanosome biogenesis. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Aug 2012]

TRAPPC6A links:

MARK4 (HGNC:13538): (microtubule affinity regulating kinase 4) This gene encodes a member of the microtubule affinity-regulating kinase family. These protein kinases phosphorylate microtubule-associated proteins and regulate the transition between stable and dynamic microtubules. The encoded protein is associated with the centrosome throughout mitosis and may be involved in cell cycle control. Expression of this gene is a potential marker for cancer, and the encoded protein may also play a role in Alzheimer's disease. Pseudogenes of this gene are located on both the short and long arm of chromosome 3. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2010]

MARK4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006273359).

BP6

Variant 19-45164934-C-T is Benign according to our data. Variant chr19-45164934-C-T is described in ClinVar as [Benign]. Clinvar id is 3037458.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.551 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRAPPC6A	NM_001270891.2 linkuse as main transcript	c.189G>A	p.Leu63=	synonymous_variant	3/6	ENST00000585934.1	NP_001257820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRAPPC6A	ENST00000585934.1 linkuse as main transcript	c.189G>A	p.Leu63=	synonymous_variant	3/6	1	NM_001270891.2	ENSP00000468612	P1	O75865-1

Frequencies

GnomAD3 genomes

AF:

0.00363

AC:

552

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0127

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000916

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00101

AC:

254

AN:

251392

Hom.:

AF XY:

0.000795

AC XY:

108

AN XY:

135886

show subpopulations

Gnomad AFR exome

AF:

0.0138

Gnomad AMR exome

AF:

0.000463

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000704

Gnomad OTH exome

AF:

0.000652

GnomAD4 exome

AF:

0.000356

AC:

521

AN:

1461820

Hom.:

Cov.:

AF XY:

0.000297

AC XY:

216

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.0128

Gnomad4 AMR exome

AF:

0.000358

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000153

Gnomad4 OTH exome

AF:

0.000861

GnomAD4 genome

AF:

0.00362

AC:

552

AN:

152340

Hom.:

Cov.:

AF XY:

0.00341

AC XY:

254

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.0127

Gnomad4 AMR

AF:

0.000915

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00232

Hom.:

Bravo

AF:

0.00406

ESP6500AA

AF:

0.0143

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00122

AC:

148

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

TRAPPC6A-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 08, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.45

CADD

Benign

9.3

DANN

Benign

0.91

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.43

T;T

MetaRNN

Benign

0.0063

T;T

MutationTaster

Benign

1.0

D;D;N;N

Sift4G

Pathogenic

0.0

D;T

Vest4

0.34

MVP

0.50

GERP RS

-3.8

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over