chr19-45172615-T-C

Variant names:

• chr19-45172615-T-C
• rs7247764
• NM_001270891.2:c.84+5520A>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+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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.36
• Publications: 10 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAPPC6A	NM_001270891.2	MANE Select	c.84+5520A>G		intron	N/A	NP_001257820.1
	TRAPPC6A	NM_024108.3		c.126+5478A>G		intron	N/A	NP_077013.1
	TRAPPC6A	NM_001270892.2		c.126+5478A>G		intron	N/A	NP_001257821.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAPPC6A	ENST00000585934.1	TSL:1 MANE Select	c.84+5520A>G		intron	N/A	ENSP00000468612.1
	TRAPPC6A	ENST00000006275.8	TSL:1	c.126+5478A>G		intron	N/A	ENSP00000006275.3
	TRAPPC6A	ENST00000592647.1	TSL:2	c.126+5478A>G		intron	N/A	ENSP00000468182.1

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35338 AN: 151256 Hom.: 5057 Cov.: 32

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.: 32 AF XY: 0.237 AC XY: 17544 AN XY: 74020

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: 67 AN: 294

European-Non Finnish (NFE) AF: 0.179 AC: 12154 AN: 67970

Other (OTH) AF: 0.193 AC: 408 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.83
DANN	Benign	0.46
PhyloP100		-3.4
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: rs7247764; hg19: chr19-45675873;