rs2010281

Positions:

• chr14-103395985-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001128918.3(MARK3):​c.52-9091G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 152,042 control chromosomes in the GnomAD database, including 6,264 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 0.26 (6264 hom., cov: 32)
• Consequence: MARK3 NM_001128918.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.185

Genes affected

MARK3 (HGNC:6897): (microtubule affinity regulating kinase 3) The protein encoded by this gene is activated by phosphorylation and in turn is involved in the phosphorylation of tau proteins MAP2 and MAP4. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

MARK3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MARK3	NM_001128918.3	c.52-9091G>A		intron_variant		ENST00000429436.7	NP_001122390.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MARK3	ENST00000429436.7	c.52-9091G>A		intron_variant		1	NM_001128918.3	ENSP00000411397.2

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39295 AN: 151924 Hom.: 6268 Cov.: 32

Gnomad AFR AF: 0.0857

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.354

Gnomad OTH AF: 0.297

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

GnomAD4 genome AF: 0.258 AC: 39280 AN: 152042 Hom.: 6264 Cov.: 32 AF XY: 0.256 AC XY: 18997 AN XY: 74316

Gnomad4 AFR AF: 0.0855

Gnomad4 AMR AF: 0.247

Gnomad4 ASJ AF: 0.450

Gnomad4 EAS AF: 0.144

Gnomad4 SAS AF: 0.338

Gnomad4 FIN AF: 0.281

Gnomad4 NFE AF: 0.354

Gnomad4 OTH AF: 0.296

Alfa AF: 0.343 Hom.: 12320

Bravo AF: 0.246

Asia WGS AF: 0.209 AC: 727 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	8.8
DANN	Benign	0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2010281; hg19: chr14-103862322;