rs774235826

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001270891.2(TRAPPC6A):c.394T>A(p.Tyr132Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000019 in 1,581,362 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

TRAPPC6A
NM_001270891.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.972

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

neurodevelopmental disorder
Inheritance: AD Classification: LIMITED Submitted by: G2P

MARK4 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 (MetaRNN=0.060331076).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001270891.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRAPPC6A	NM_001270891.2	MANE Select	c.394T>A	p.Tyr132Asn	missense	Exon 5 of 6	NP_001257820.1	O75865-1
TRAPPC6A	NM_024108.3		c.436T>A	p.Tyr146Asn	missense	Exon 5 of 6	NP_077013.1	O75865-2
TRAPPC6A	NM_001270892.2		c.368T>A	p.Leu123Gln	missense	Exon 4 of 5	NP_001257821.1	O75865-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRAPPC6A	ENST00000585934.1	TSL:1 MANE Select	c.394T>A	p.Tyr132Asn	missense	Exon 5 of 6	ENSP00000468612.1	O75865-1
TRAPPC6A	ENST00000006275.8	TSL:1	c.436T>A	p.Tyr146Asn	missense	Exon 5 of 6	ENSP00000006275.3	O75865-2
TRAPPC6A	ENST00000940426.1		c.352T>A	p.Tyr118Asn	missense	Exon 4 of 5	ENSP00000610485.1

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152026

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000945

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000883

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000103

AC:

AN:

194912

AF XY:

0.00000962

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:

0.0000236

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000154

AC:

AN:

1429336

Hom.:

Cov.:

AF XY:

0.0000170

AC XY:

AN XY:

707568

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33230

American (AMR)

AF:

0.00

AC:

AN:

38300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25376

East Asian (EAS)

AF:

0.00

AC:

AN:

38638

South Asian (SAS)

AF:

0.00

AC:

AN:

81312

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51178

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5726

European-Non Finnish (NFE)

AF:

0.0000192

AC:

AN:

1096248

Other (OTH)

AF:

0.0000169

AC:

AN:

59328

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

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:

0.0000526

AC:

AN:

152026

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74270

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41412

American (AMR)

AF:

0.00

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0000945

AC:

AN:

10578

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000883

AC:

AN:

67972

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

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:

0.0000900

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000167

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.71

CADD

Benign

5.9

(source)

DANN

Benign

0.87

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.36

M_CAP

Benign

0.0036

MetaRNN

Benign

0.060

PhyloP100

-0.97

Vest4

0.090

MVP

0.061

ClinPred

0.24

GERP RS

-0.28

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.31

Mutation Taster

=84/16

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