rs12460041

Variant names:

• chr19-45174057-T-C
• rs12460041
• NM_001270891.2:c.84+4078A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001270891.2(TRAPPC6A):​c.84+4078A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 152,180 control chromosomes in the GnomAD database, including 1,004 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 0.10 (1004 hom., cov: 31)
• Consequence: TRAPPC6A NM_001270891.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46
• Publications: 14 publications found

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]

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAPPC6A	NM_001270891.2	c.84+4078A>G		intron_variant	Intron 1 of 5	ENST00000585934.1	NP_001257820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAPPC6A	ENST00000585934.1	c.84+4078A>G		intron_variant	Intron 1 of 5	1	NM_001270891.2	ENSP00000468612.1

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15939 AN: 152062 Hom.: 1002 Cov.: 31

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.00881

Gnomad AMR AF: 0.0565

Gnomad ASJ AF: 0.0767

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0792

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0980

Gnomad OTH AF: 0.0891

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

GnomAD4 genome AF: 0.105 AC: 15952 AN: 152180 Hom.: 1004 Cov.: 31 AF XY: 0.106 AC XY: 7892 AN XY: 74404

African (AFR) AF: 0.144 AC: 5975 AN: 41506

American (AMR) AF: 0.0564 AC: 863 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0767 AC: 266 AN: 3466

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5178

South Asian (SAS) AF: 0.0792 AC: 382 AN: 4822

European-Finnish (FIN) AF: 0.148 AC: 1565 AN: 10596

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.0980 AC: 6662 AN: 68010

Other (OTH) AF: 0.0877 AC: 185 AN: 2110

Alfa AF: 0.102 Hom.: 521

Bravo AF: 0.0978

Asia WGS AF: 0.0360 AC: 124 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	9.0
DANN	Benign	0.83
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12460041; hg19: chr19-45677315;