19-45296184-T-C

Variant names:

• chr19-45296184-T-C
• rs344807
• NM_001199867.2:c.1599-1492T>C

Variant summary

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

The NM_001199867.2(MARK4):​c.1599-1492T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.689 in 151,932 control chromosomes in the GnomAD database, including 37,343 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 0.69 (37343 hom., cov: 31)
• Consequence: MARK4 NM_001199867.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.19
• Publications: 14 publications found

Genes affected

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.811 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001199867.2. 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
	MARK4	NM_001199867.2	MANE Select	c.1599-1492T>C		intron	N/A	NP_001186796.1
	MARK4	NM_031417.4		c.1599-1492T>C		intron	N/A	NP_113605.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MARK4	ENST00000262891.9	TSL:1 MANE Select	c.1599-1492T>C		intron	N/A	ENSP00000262891.3
	MARK4	ENST00000300843.8	TSL:1	c.1599-1492T>C		intron	N/A	ENSP00000300843.3

Frequencies

GnomAD3 genomes AF: 0.689 AC: 104591 AN: 151814 Hom.: 37308 Cov.: 31

Gnomad AFR AF: 0.818

Gnomad AMI AF: 0.781

Gnomad AMR AF: 0.495

Gnomad ASJ AF: 0.661

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.629

Gnomad FIN AF: 0.681

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.694

Gnomad OTH AF: 0.665

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

GnomAD4 genome AF: 0.689 AC: 104674 AN: 151932 Hom.: 37343 Cov.: 31 AF XY: 0.681 AC XY: 50581 AN XY: 74262

African (AFR) AF: 0.818 AC: 33904 AN: 41452

American (AMR) AF: 0.495 AC: 7548 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.661 AC: 2292 AN: 3468

East Asian (EAS) AF: 0.246 AC: 1266 AN: 5148

South Asian (SAS) AF: 0.627 AC: 3016 AN: 4812

European-Finnish (FIN) AF: 0.681 AC: 7173 AN: 10530

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.694 AC: 47164 AN: 67948

Other (OTH) AF: 0.667 AC: 1404 AN: 2106

Alfa AF: 0.684 Hom.: 113772

Bravo AF: 0.675

Asia WGS AF: 0.492 AC: 1717 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	0.13
DANN	Benign	0.60
PhyloP100		-3.2
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: rs344807; hg19: chr19-45799442;