Variant 14-103457138-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001128918.3(MARK3):c.413-4A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 1,572,776 control chromosomes in the GnomAD database, including 91,062 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.34 ( 8876 hom., cov: 33)

Exomes 𝑓: 0.33 ( 82186 hom. )

Consequence

MARK3
NM_001128918.3 splice_region, intron

Scores

Splicing: ADA: 0.00008239

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0430

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 14-103457138-A-G is Benign according to our data. Variant chr14-103457138-A-G is described in ClinVar as [Benign]. Clinvar id is 1321158.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MARK3	NM_001128918.3 link	c.413-4A>G		splice_region_variant, intron_variant	Intron 5 of 17	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.413-4A>G		splice_region_variant, intron_variant	Intron 5 of 17	1	NM_001128918.3	ENSP00000411397.2		P27448-5

Frequencies

GnomAD3 genomes

AF:

0.335

AC:

50969

AN:

152036

Hom.:

8872

Cov.:

show subpopulations

Gnomad AFR

AF:

0.352

Gnomad AMI

AF:

0.277

Gnomad AMR

AF:

0.276

Gnomad ASJ

AF:

0.454

Gnomad EAS

AF:

0.144

Gnomad SAS

AF:

0.338

Gnomad FIN

AF:

0.282

Gnomad MID

AF:

0.459

Gnomad NFE

AF:

0.355

Gnomad OTH

AF:

0.342

GnomAD3 exomes

AF:

0.314

AC:

78038

AN:

248170

Hom.:

13210

AF XY:

0.323

AC XY:

43482

AN XY:

134700

show subpopulations

Gnomad AFR exome

AF:

0.343

Gnomad AMR exome

AF:

0.200

Gnomad ASJ exome

AF:

0.435

Gnomad EAS exome

AF:

0.126

Gnomad SAS exome

AF:

0.346

Gnomad FIN exome

AF:

0.295

Gnomad NFE exome

AF:

0.359

Gnomad OTH exome

AF:

0.332

GnomAD4 exome

AF:

0.335

AC:

475427

AN:

1420622

Hom.:

82186

Cov.:

AF XY:

0.337

AC XY:

239278

AN XY:

709194

show subpopulations

Gnomad4 AFR exome

AF:

0.347

Gnomad4 AMR exome

AF:

0.209

Gnomad4 ASJ exome

AF:

0.439

Gnomad4 EAS exome

AF:

0.162

Gnomad4 SAS exome

AF:

0.351

Gnomad4 FIN exome

AF:

0.303

Gnomad4 NFE exome

AF:

0.343

Gnomad4 OTH exome

AF:

0.339

GnomAD4 genome

AF:

0.335

AC:

50988

AN:

152154

Hom.:

8876

Cov.:

AF XY:

0.330

AC XY:

24556

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.352

Gnomad4 AMR

AF:

0.276

Gnomad4 ASJ

AF:

0.454

Gnomad4 EAS

AF:

0.144

Gnomad4 SAS

AF:

0.339

Gnomad4 FIN

AF:

0.282

Gnomad4 NFE

AF:

0.355

Gnomad4 OTH

AF:

0.340

Alfa

AF:

0.351

Hom.:

5916

Bravo

AF:

0.333

Asia WGS

AF:

0.226

AC:

788

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

MARK3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 22, 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). -

Visual impairment and progressive phthisis bulbi

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.77

DANN

Benign

0.44

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000082

dbscSNV1_RF

Benign

0.030

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