19-45296184-T-C

Position:

• chr19-45296184-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MARK4	NM_001199867.2	c.1599-1492T>C		intron_variant		ENST00000262891.9	NP_001186796.1
MARK4	NM_031417.4	c.1599-1492T>C		intron_variant			NP_113605.2
MARK4	XM_006723307.5	c.1398-1492T>C		intron_variant			XP_006723370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MARK4	ENST00000262891.9	c.1599-1492T>C		intron_variant		1	NM_001199867.2	ENSP00000262891.3
MARK4	ENST00000300843.8	c.1599-1492T>C		intron_variant		1		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

Gnomad4 AFR AF: 0.818

Gnomad4 AMR AF: 0.495

Gnomad4 ASJ AF: 0.661

Gnomad4 EAS AF: 0.246

Gnomad4 SAS AF: 0.627

Gnomad4 FIN AF: 0.681

Gnomad4 NFE AF: 0.694

Gnomad4 OTH AF: 0.667

Alfa AF: 0.679 Hom.: 72993

Bravo AF: 0.675

Asia WGS AF: 0.492 AC: 1717 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	0.13
DANN	Benign	0.60

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

LitVar

Other links and lift over

dbSNP: rs344807; hg19: chr19-45799442;