Variant 14-103405175-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000429436.7(MARK3):c.151C>T(p.Pro51Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

MARK3
ENST00000429436.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.85

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MARK3	NM_001128918.3 linkuse as main transcript	c.151C>T	p.Pro51Ser	missense_variant	2/18	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.151C>T	p.Pro51Ser	missense_variant	2/18	1	NM_001128918.3	ENSP00000411397	P1	P27448-5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000432

AC:

AN:

231650

Hom.:

AF XY:

0.00

AC XY:

AN XY:

126038

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00000926

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000712

Hom.:

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

Oct 17, 2023

The c.151C>T (p.P51S) alteration is located in exon 2 (coding exon 2) of the MARK3 gene. This alteration results from a C to T substitution at nucleotide position 151, causing the proline (P) at amino acid position 51 to be replaced by a serine (S). 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

0.87

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

-0.020

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.65

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

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Uncertain

0.94

LIST_S2

Pathogenic

0.99

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

M_CAP

Uncertain

0.092

MetaRNN

Uncertain

0.71

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

MetaSVM

Uncertain

0.29

MutationAssessor

Benign

0.26

N;N;N;N;N;N;.;.;.

MutationTaster

Benign

0.66

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

PrimateAI

Uncertain

0.77

PROVEAN

Pathogenic

-6.7

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

REVEL

Uncertain

0.42

Sift

Benign

0.036

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

Sift4G

Uncertain

0.026

D;T;T;T;T;T;T;T;T

Polyphen

1.0, 0.99, 1.0

.;D;D;D;D;D;.;.;.

Vest4

0.84

MutPred

0.35

Gain of catalytic residue at Y56 (P = 0.0064);Gain of catalytic residue at Y56 (P = 0.0064);Gain of catalytic residue at Y56 (P = 0.0064);Gain of catalytic residue at Y56 (P = 0.0064);Gain of catalytic residue at Y56 (P = 0.0064);Gain of catalytic residue at Y56 (P = 0.0064);Gain of catalytic residue at Y56 (P = 0.0064);Gain of catalytic residue at Y56 (P = 0.0064);.;

MVP

0.88

MPC

1.0

ClinPred

0.95

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.85

gMVP

0.53

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

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

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