rs1989565

Variant names:

• chr14-103395856-G-A
• rs1989565
• NM_001128918.3:c.52-9220G>A

Your query was ambiguous. Multiple possible variants found:

• chr14-103395856-G-A
• chr14-103395856-G-T

Variant summary

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

The NM_001128918.3(MARK3):​c.52-9220G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.676 in 151,958 control chromosomes in the GnomAD database, including 35,068 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 0.68 (35068 hom., cov: 31)
• Consequence: MARK3 NM_001128918.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.536
• Publications: 8 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.835 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MARK3	NM_001128918.3	c.52-9220G>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.52-9220G>A		intron_variant	Intron 1 of 17	1	NM_001128918.3	ENSP00000411397.2

Frequencies

GnomAD3 genomes AF: 0.676 AC: 102686 AN: 151840 Hom.: 35036 Cov.: 31

Gnomad AFR AF: 0.699

Gnomad AMI AF: 0.723

Gnomad AMR AF: 0.725

Gnomad ASJ AF: 0.543

Gnomad EAS AF: 0.856

Gnomad SAS AF: 0.658

Gnomad FIN AF: 0.718

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.641

Gnomad OTH AF: 0.645

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

GnomAD4 genome AF: 0.676 AC: 102766 AN: 151958 Hom.: 35068 Cov.: 31 AF XY: 0.680 AC XY: 50512 AN XY: 74282

African (AFR) AF: 0.698 AC: 28926 AN: 41416

American (AMR) AF: 0.725 AC: 11066 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.543 AC: 1882 AN: 3468

East Asian (EAS) AF: 0.857 AC: 4435 AN: 5178

South Asian (SAS) AF: 0.657 AC: 3166 AN: 4818

European-Finnish (FIN) AF: 0.718 AC: 7588 AN: 10562

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.641 AC: 43521 AN: 67942

Other (OTH) AF: 0.647 AC: 1367 AN: 2114

Alfa AF: 0.648 Hom.: 3328

Bravo AF: 0.680

Asia WGS AF: 0.769 AC: 2673 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	4.2
DANN	Benign	0.74
PhyloP100		-0.54
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: rs1989565; hg19: chr14-103862193;