Genetic Variant MAP4:p.Arg23Gln (chr3-47998793-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001385682.1(MAP4):c.68G>A(p.Arg23Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0662 in 1,613,960 control chromosomes in the GnomAD database, including 4,031 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.047 ( 222 hom., cov: 32)

Exomes 𝑓: 0.068 ( 3809 hom. )

Consequence

MAP4
NM_001385682.1 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.53

Variant links:

Genes affected

MAP4 (HGNC:6862): (microtubule associated protein 4) The protein encoded by this gene is a major non-neuronal microtubule-associated protein. This protein contains a domain similar to the microtubule-binding domains of neuronal microtubule-associated protein (MAP2) and microtubule-associated protein tau (MAPT/TAU). This protein promotes microtubule assembly, and has been shown to counteract destabilization of interphase microtubule catastrophe promotion. Cyclin B was found to interact with this protein, which targets cell division cycle 2 (CDC2) kinase to microtubules. The phosphorylation of this protein affects microtubule properties and cell cycle progression. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]

MAP4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0023638904).

BP6

Variant 3-47998793-C-T is Benign according to our data. Variant chr3-47998793-C-T is described in ClinVar as [Benign]. Clinvar id is 3056736.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP4	NM_001385682.1 link	c.68G>A	p.Arg23Gln	missense_variant	Exon 2 of 21	ENST00000683076.1	NP_001372611.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP4	ENST00000683076.1 link	c.68G>A	p.Arg23Gln	missense_variant	Exon 2 of 21		NM_001385682.1	ENSP00000507895.1		A0A804HKE7

Frequencies

GnomAD3 genomes

AF:

0.0468

AC:

7124

AN:

152164

Hom.:

222

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0141

Gnomad AMI

AF:

0.0473

Gnomad AMR

AF:

0.0338

Gnomad ASJ

AF:

0.0504

Gnomad EAS

AF:

0.000963

Gnomad SAS

AF:

0.0499

Gnomad FIN

AF:

0.0416

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0734

Gnomad OTH

AF:

0.0478

GnomAD3 exomes

AF:

0.0526

AC:

13217

AN:

251290

Hom.:

470

AF XY:

0.0553

AC XY:

7514

AN XY:

135808

show subpopulations

Gnomad AFR exome

AF:

0.0111

Gnomad AMR exome

AF:

0.0233

Gnomad ASJ exome

AF:

0.0556

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.0496

Gnomad FIN exome

AF:

0.0415

Gnomad NFE exome

AF:

0.0781

Gnomad OTH exome

AF:

0.0623

GnomAD4 exome

AF:

0.0682

AC:

99679

AN:

1461678

Hom.:

3809

Cov.:

AF XY:

0.0683

AC XY:

49638

AN XY:

727134

show subpopulations

Gnomad4 AFR exome

AF:

0.0100

Gnomad4 AMR exome

AF:

0.0260

Gnomad4 ASJ exome

AF:

0.0542

Gnomad4 EAS exome

AF:

0.000227

Gnomad4 SAS exome

AF:

0.0492

Gnomad4 FIN exome

AF:

0.0459

Gnomad4 NFE exome

AF:

0.0773

Gnomad4 OTH exome

AF:

0.0599

GnomAD4 genome

AF:

0.0468

AC:

7122

AN:

152282

Hom.:

222

Cov.:

AF XY:

0.0442

AC XY:

3293

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0141

Gnomad4 AMR

AF:

0.0337

Gnomad4 ASJ

AF:

0.0504

Gnomad4 EAS

AF:

0.000965

Gnomad4 SAS

AF:

0.0504

Gnomad4 FIN

AF:

0.0416

Gnomad4 NFE

AF:

0.0734

Gnomad4 OTH

AF:

0.0468

Alfa

AF:

0.0685

Hom.:

798

Bravo

AF:

0.0443

TwinsUK

AF:

0.0831

AC:

308

ALSPAC

AF:

0.0675

AC:

260

ESP6500AA

AF:

0.0168

AC:

ESP6500EA

AF:

0.0781

AC:

672

ExAC

AF:

0.0546

AC:

6635

Asia WGS

AF:

0.0200

AC:

AN:

3478

EpiCase

AF:

0.0764

EpiControl

AF:

0.0776

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MAP4-related disorder

Benign:1

Dec 04, 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

AlphaMissense

Benign

0.34

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.042

.;T;T;T;.;.;.;.

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.79

LIST_S2

Uncertain

0.93

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

MetaRNN

Benign

0.0024

T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

M;.;M;.;.;M;M;.

PrimateAI

Uncertain

0.48

PROVEAN

Benign

-2.1

N;N;N;.;.;D;D;.

REVEL

Benign

0.11

Sift

Benign

0.037

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

Sift4G

Benign

0.39

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

Polyphen

1.0

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

Vest4

0.29

MPC

0.53

ClinPred

0.027

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.19

gMVP

0.033

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