Genetic Variant MAP4:p.Ile2126Thr (chr3-47869245-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001385682.1(MAP4):c.6377T>C(p.Ile2126Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,622 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

MAP4
NM_001385682.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.891

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.121338844).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001385682.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAP4	NM_001385682.1	MANE Select	c.6377T>C	p.Ile2126Thr	missense	Exon 16 of 21	NP_001372611.1	A0A804HKE7
MAP4	NM_001385687.1		c.6377T>C	p.Ile2126Thr	missense	Exon 16 of 21	NP_001372616.1
MAP4	NM_001384745.1		c.3029T>C	p.Ile1010Thr	missense	Exon 16 of 21	NP_001371674.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAP4	ENST00000683076.1	MANE Select	c.6377T>C	p.Ile2126Thr	missense	Exon 16 of 21	ENSP00000507895.1	A0A804HKE7
MAP4	ENST00000360240.10	TSL:1	c.2942T>C	p.Ile981Thr	missense	Exon 14 of 19	ENSP00000353375.6	P27816-1
MAP4	ENST00000429422.5	TSL:1	c.1089+1568T>C		intron	N/A	ENSP00000416743.1	H7C4C5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461622

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727136

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111774

Other (OTH)

AF:

0.00

AC:

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.036

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.81

M_CAP

Benign

0.0056

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

PhyloP100

0.89

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.082

Sift

Uncertain

0.010

Sift4G

Benign

0.34

Polyphen

0.94

Vest4

0.11

MutPred

0.15

Loss of glycosylation at K976 (P = 0.0437)

MVP

0.12

MPC

0.27

ClinPred

0.33

GERP RS

0.38

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.086

gMVP

0.059

Mutation Taster

=95/5

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over