rs2010281

Variant names:

• chr14-103395985-G-A
• rs2010281
• NM_001128918.3:c.52-9091G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 37 publications found

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 Gene-Disease associations (from GenCC):

• visual impairment and progressive phthisis bulbi

  Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MARK3	NM_001128918.3	c.52-9091G>A		intron_variant	Intron 1 of 17	ENST00000429436.7	NP_001122390.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MARK3	ENST00000429436.7	c.52-9091G>A		intron_variant	Intron 1 of 17	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

African (AFR) AF: 0.0855 AC: 3548 AN: 41496

American (AMR) AF: 0.247 AC: 3775 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.450 AC: 1561 AN: 3468

East Asian (EAS) AF: 0.144 AC: 742 AN: 5160

South Asian (SAS) AF: 0.338 AC: 1630 AN: 4818

European-Finnish (FIN) AF: 0.281 AC: 2967 AN: 10570

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.354 AC: 24051 AN: 67956

Other (OTH) AF: 0.296 AC: 625 AN: 2112

Alfa AF: 0.333 Hom.: 14961

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
PhyloP100		-0.18
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2010281; hg19: chr14-103862322;