Genetic Variant MAP4:c.*69G>A (chr3-47852865-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_001134364.2(MAP4):c.3335G>A(p.Arg1112His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000284 in 1,569,108 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00029 ( 0 hom. )

Consequence

MAP4
NM_001134364.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.49

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07937989).

BP6

Variant 3-47852865-C-T is Benign according to our data. Variant chr3-47852865-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2653784.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP4	NM_001385682.1 link	c.*69G>A		3_prime_UTR_variant	Exon 21 of 21	ENST00000683076.1	NP_001372611.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP4	ENST00000683076 link	c.*69G>A		3_prime_UTR_variant	Exon 21 of 21		NM_001385682.1	ENSP00000507895.1		A0A804HKE7

Frequencies

GnomAD3 genomes

AF:

0.000217

AC:

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000209

AC:

AN:

176950

Hom.:

AF XY:

0.000219

AC XY:

AN XY:

95674

show subpopulations

Gnomad AFR exome

AF:

0.000102

Gnomad AMR exome

AF:

0.000153

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000398

Gnomad FIN exome

AF:

0.0000590

Gnomad NFE exome

AF:

0.000385

Gnomad OTH exome

AF:

0.000418

GnomAD4 exome

AF:

0.000291

AC:

412

AN:

1416826

Hom.:

Cov.:

AF XY:

0.000291

AC XY:

204

AN XY:

701260

show subpopulations

Gnomad4 AFR exome

AF:

0.0000311

Gnomad4 AMR exome

AF:

0.000189

Gnomad4 ASJ exome

AF:

0.0000395

Gnomad4 EAS exome

AF:

0.0000272

Gnomad4 SAS exome

AF:

0.0000612

Gnomad4 FIN exome

AF:

0.0000397

Gnomad4 NFE exome

AF:

0.000343

Gnomad4 OTH exome

AF:

0.000323

GnomAD4 genome

AF:

0.000217

AC:

AN:

152282

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000353

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000303

Hom.:

Bravo

AF:

0.000215

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.000110

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

MAP4: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

1.0

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.65

T;T;T

M_CAP

Benign

0.028

MetaRNN

Benign

0.079

T;T;T

MetaSVM

Benign

-0.88

PROVEAN

Benign

-0.49

N;N;N

REVEL

Benign

0.096

Sift

Benign

0.21

T;T;T

Sift4G

Benign

0.090

T;T;T

Polyphen

1.0

D;D;.

Vest4

0.25

MVP

0.44

ClinPred

0.026

GERP RS

3.8

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