dbSNP rs7247764: TRAPPC6A:c.84+5520A>G (chr19-45172615-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001270891.2(TRAPPC6A):c.84+5520A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 151,374 control chromosomes in the GnomAD database, including 5,072 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.23 ( 5072 hom., cov: 32)

Consequence

TRAPPC6A
NM_001270891.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.36

Publications

10 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.02).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAPPC6A	NM_001270891.2 link	c.84+5520A>G		intron_variant	Intron 1 of 5	ENST00000585934.1	NP_001257820.1	O75865-1B7TZ90

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAPPC6A	ENST00000585934.1 link	c.84+5520A>G		intron_variant	Intron 1 of 5	1	NM_001270891.2	ENSP00000468612.1		O75865-1

Frequencies

GnomAD3 genomes

AF:

0.234

AC:

35338

AN:

151256

Hom.:

5057

Cov.:

show subpopulations

Gnomad AFR

AF:

0.355

Gnomad AMI

AF:

0.0614

Gnomad AMR

AF:

0.195

Gnomad ASJ

AF:

0.144

Gnomad EAS

AF:

0.133

Gnomad SAS

AF:

0.225

Gnomad FIN

AF:

0.284

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.179

Gnomad OTH

AF:

0.192

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.234

AC:

35395

AN:

151374

Hom.:

5072

Cov.:

AF XY:

0.237

AC XY:

17544

AN XY:

74020

show subpopulations

African (AFR)

AF:

0.354

AC:

14444

AN:

40758

American (AMR)

AF:

0.196

AC:

2990

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.144

AC:

499

AN:

3472

East Asian (EAS)

AF:

0.133

AC:

689

AN:

5186

South Asian (SAS)

AF:

0.224

AC:

1079

AN:

4816

European-Finnish (FIN)

AF:

0.284

AC:

3009

AN:

10610

Middle Eastern (MID)

AF:

0.228

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.179

AC:

12154

AN:

67970

Other (OTH)

AF:

0.193

AC:

408

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1291

2582

3872

5163

6454

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

370

740

1110

1480

1850

<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:

0.196

Hom.:

2961

Bravo

AF:

0.231

Asia WGS

AF:

0.177

AC:

613

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.83

(source)

DANN

Benign

0.46

PhyloP100

-3.4

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over