Genetic Variant MARK3:p.Thr438Thr (chr14-103475042-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BA1

The NM_001128918.3(MARK3):c.1314C>A(p.Thr438Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00798 in 1,614,042 control chromosomes in the GnomAD database, including 949 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.044 ( 512 hom., cov: 33)

Exomes 𝑓: 0.0043 ( 437 hom. )

Consequence

MARK3
NM_001128918.3 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.06

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.035).

BP6

Variant 14-103475042-C-A is Benign according to our data. Variant chr14-103475042-C-A is described in ClinVar as [Benign]. Clinvar id is 3055758.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=1.06 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MARK3	NM_001128918.3 link	c.1314C>A	p.Thr438Thr	synonymous_variant	Exon 13 of 18	ENST00000429436.7	NP_001122390.2	P27448-5Q86U11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MARK3	ENST00000429436.7 link	c.1314C>A	p.Thr438Thr	synonymous_variant	Exon 13 of 18	1	NM_001128918.3	ENSP00000411397.2		P27448-5

Frequencies

GnomAD3 genomes

AF:

0.0436

AC:

6632

AN:

152120

Hom.:

510

Cov.:

show subpopulations

Gnomad AFR

AF:

0.154

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0135

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.0206

GnomAD2 exomes

AF:

0.0108

AC:

2686

AN:

249504

AF XY:

0.00790

show subpopulations

Gnomad AFR exome

AF:

0.155

Gnomad AMR exome

AF:

0.00678

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000185

Gnomad OTH exome

AF:

0.00363

GnomAD4 exome

AF:

0.00427

AC:

6236

AN:

1461804

Hom.:

437

Cov.:

AF XY:

0.00363

AC XY:

2641

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.155

AC:

5179

AN:

33424

Gnomad4 AMR exome

AF:

0.00776

AC:

347

AN:

44722

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

26136

Gnomad4 EAS exome

AF:

0.0000252

AC:

AN:

39700

Gnomad4 SAS exome

AF:

0.000255

AC:

AN:

86256

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

53418

Gnomad4 NFE exome

AF:

0.0000818

AC:

AN:

1111994

Gnomad4 Remaining exome

AF:

0.00947

AC:

572

AN:

60386

Heterozygous variant carriers

261

522

782

1043

1304

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

154

308

462

616

770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0437

AC:

6649

AN:

152238

Hom.:

512

Cov.:

AF XY:

0.0416

AC XY:

3095

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.154

AC:

0.153574

AN:

0.153574

Gnomad4 AMR

AF:

0.0134

AC:

0.0134145

AN:

0.0134145

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.000207

AC:

0.000207039

AN:

0.000207039

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.000338

AC:

0.000338146

AN:

0.000338146

Gnomad4 OTH

AF:

0.0203

AC:

0.0203406

AN:

0.0203406

Heterozygous variant carriers

298

596

893

1191

1489

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

128

192

256

320

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0199

Hom.:

140

Bravo

AF:

0.0494

Asia WGS

AF:

0.00895

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MARK3-related disorder

Benign:1

Sep 30, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.29

CADD

Benign

7.7

DANN

Benign

0.41

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

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