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14-103475117-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_001128918.3(MARK3):c.1389G>A(p.Lys463=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0124 in 1,614,090 control chromosomes in the GnomAD database, including 167 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.011 ( 28 hom., cov: 33)
Exomes 𝑓: 0.013 ( 139 hom. )

Consequence

MARK3
NM_001128918.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.54
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.32).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 14-103475117-G-A is Benign according to our data. Variant chr14-103475117-G-A is described in ClinVar as [Benign]. Clinvar id is 3044255.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=2.54 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 28 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MARK3NM_001128918.3 linkuse as main transcriptc.1389G>A p.Lys463= synonymous_variant 13/18 ENST00000429436.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MARK3ENST00000429436.7 linkuse as main transcriptc.1389G>A p.Lys463= synonymous_variant 13/181 NM_001128918.3 P1P27448-5

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0106
AC:
1612
AN:
152222
Hom.:
28
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00191
Gnomad AMI
AF:
0.00110
Gnomad AMR
AF:
0.00320
Gnomad ASJ
AF:
0.000864
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.00145
Gnomad FIN
AF:
0.0477
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0139
Gnomad OTH
AF:
0.00956
GnomAD3 exomes
AF:
0.0115
AC:
2871
AN:
249524
Hom.:
30
AF XY:
0.0112
AC XY:
1518
AN XY:
135382
show subpopulations
Gnomad AFR exome
AF:
0.00233
Gnomad AMR exome
AF:
0.00235
Gnomad ASJ exome
AF:
0.00139
Gnomad EAS exome
AF:
0.0000557
Gnomad SAS exome
AF:
0.00284
Gnomad FIN exome
AF:
0.0463
Gnomad NFE exome
AF:
0.0140
Gnomad OTH exome
AF:
0.0114
GnomAD4 exome
AF:
0.0126
AC:
18480
AN:
1461750
Hom.:
139
Cov.:
31
AF XY:
0.0124
AC XY:
9038
AN XY:
727180
show subpopulations
Gnomad4 AFR exome
AF:
0.00170
Gnomad4 AMR exome
AF:
0.00259
Gnomad4 ASJ exome
AF:
0.00199
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00279
Gnomad4 FIN exome
AF:
0.0484
Gnomad4 NFE exome
AF:
0.0133
Gnomad4 OTH exome
AF:
0.0100
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0106
AC:
1612
AN:
152340
Hom.:
28
Cov.:
33
AF XY:
0.0117
AC XY:
869
AN XY:
74500
show subpopulations
Gnomad4 AFR
AF:
0.00190
Gnomad4 AMR
AF:
0.00320
Gnomad4 ASJ
AF:
0.000864
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00145
Gnomad4 FIN
AF:
0.0477
Gnomad4 NFE
AF:
0.0139
Gnomad4 OTH
AF:
0.00946
Alfa
AF:
0.0121
Hom.:
7
Bravo
AF:
0.00697
Asia WGS
AF:
0.00173
AC:
6
AN:
3478
EpiCase
AF:
0.0109
EpiControl
AF:
0.0112

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

MARK3-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesJun 25, 2019This 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
-0.32
Cadd
Benign
8.4
Dann
Benign
0.59
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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.

Other links and lift over

dbSNP: rs56126530; hg19: chr14-103941454; API