Variant 14-103475042-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BA1

The ENST00000429436.7(MARK3):c.1314C>A(p.Thr438=) 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
ENST00000429436.7 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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.29).

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/exons	MANE	Protein	UniProt
MARK3	NM_001128918.3 linkuse as main transcript	c.1314C>A	p.Thr438=	synonymous_variant	13/18	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.1314C>A	p.Thr438=	synonymous_variant	13/18	1	NM_001128918.3	ENSP00000411397	P1	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

GnomAD3 exomes

AF:

0.0108

AC:

2686

AN:

249504

Hom.:

204

AF XY:

0.00790

AC XY:

1069

AN XY:

135380

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 SAS exome

AF:

0.000163

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

Gnomad4 AMR exome

AF:

0.00776

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000255

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000818

Gnomad4 OTH exome

AF:

0.00947

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

Gnomad4 AMR

AF:

0.0134

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000338

Gnomad4 OTH

AF:

0.0203

Alfa

AF:

0.0194

Hom.:

106

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

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 30, 2019

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

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