Variant 14-103386055-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000429436.7(MARK3):c.26C>T(p.Thr9Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

MARK3
ENST00000429436.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.07

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3781928).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MARK3	NM_001128918.3 linkuse as main transcript	c.26C>T	p.Thr9Met	missense_variant	1/18	ENST00000429436.7	NP_001122390.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MARK3	ENST00000429436.7 linkuse as main transcript	c.26C>T	p.Thr9Met	missense_variant	1/18	1	NM_001128918.3	ENSP00000411397	P1	P27448-5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249528

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135394

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461822

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 01, 2024

The c.26C>T (p.T9M) alteration is located in exon 1 (coding exon 1) of the MARK3 gene. This alteration results from a C to T substitution at nucleotide position 26, causing the threonine (T) at amino acid position 9 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.81

BayesDel_addAF

Benign

-0.047

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.59

.;.;D;.;.;.;T;.

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Benign

0.11

LIST_S2

Pathogenic

0.99

D;D;D;D;D;D;D;D

M_CAP

Pathogenic

0.36

MetaRNN

Benign

0.38

T;T;T;T;T;T;T;T

MetaSVM

Uncertain

0.069

MutationAssessor

Uncertain

2.3

M;M;M;M;M;M;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D;N

PrimateAI

Pathogenic

0.87

PROVEAN

Uncertain

-2.8

D;D;D;D;D;D;D;D

REVEL

Benign

0.28

Sift

Uncertain

0.0010

D;D;D;D;D;D;D;D

Sift4G

Uncertain

0.015

D;D;D;D;D;D;D;D

Polyphen

0.93, 0.88, 0.16, 0.96

.;P;P;B;P;D;.;.

Vest4

0.44

MutPred

0.22

Gain of catalytic residue at R4 (P = 0.0056);Gain of catalytic residue at R4 (P = 0.0056);Gain of catalytic residue at R4 (P = 0.0056);Gain of catalytic residue at R4 (P = 0.0056);Gain of catalytic residue at R4 (P = 0.0056);Gain of catalytic residue at R4 (P = 0.0056);Gain of catalytic residue at R4 (P = 0.0056);Gain of catalytic residue at R4 (P = 0.0056);

MVP

0.84

MPC

0.69

ClinPred

0.98

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.19

gMVP

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over