3-47867325-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001385682.1(MAP4):​c.6422C>T​(p.Ser2141Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00437 in 1,611,796 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0034 ( 2 hom., cov: 32)
Exomes 𝑓: 0.0045 ( 28 hom. )

Consequence

MAP4
NM_001385682.1 missense

Scores

5
10
4

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 4.19
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.011303484).
BP6
Variant 3-47867325-G-A is Benign according to our data. Variant chr3-47867325-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3039009.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MAP4NM_001385682.1 linkuse as main transcriptc.6422C>T p.Ser2141Phe missense_variant 17/21 ENST00000683076.1 NP_001372611.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MAP4ENST00000683076.1 linkuse as main transcriptc.6422C>T p.Ser2141Phe missense_variant 17/21 NM_001385682.1 ENSP00000507895 A2

Frequencies

GnomAD3 genomes
AF:
0.00345
AC:
524
AN:
152100
Hom.:
2
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00104
Gnomad AMI
AF:
0.0143
Gnomad AMR
AF:
0.00544
Gnomad ASJ
AF:
0.000576
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.00186
Gnomad FIN
AF:
0.000378
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.00525
Gnomad OTH
AF:
0.00526
GnomAD3 exomes
AF:
0.00311
AC:
780
AN:
251178
Hom.:
4
AF XY:
0.00328
AC XY:
445
AN XY:
135758
show subpopulations
Gnomad AFR exome
AF:
0.000800
Gnomad AMR exome
AF:
0.00284
Gnomad ASJ exome
AF:
0.000695
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00173
Gnomad FIN exome
AF:
0.000370
Gnomad NFE exome
AF:
0.00509
Gnomad OTH exome
AF:
0.00359
GnomAD4 exome
AF:
0.00447
AC:
6527
AN:
1459578
Hom.:
28
Cov.:
29
AF XY:
0.00453
AC XY:
3293
AN XY:
726284
show subpopulations
Gnomad4 AFR exome
AF:
0.000629
Gnomad4 AMR exome
AF:
0.00307
Gnomad4 ASJ exome
AF:
0.000727
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00163
Gnomad4 FIN exome
AF:
0.000374
Gnomad4 NFE exome
AF:
0.00531
Gnomad4 OTH exome
AF:
0.00449
GnomAD4 genome
AF:
0.00344
AC:
523
AN:
152218
Hom.:
2
Cov.:
32
AF XY:
0.00355
AC XY:
264
AN XY:
74412
show subpopulations
Gnomad4 AFR
AF:
0.00104
Gnomad4 AMR
AF:
0.00543
Gnomad4 ASJ
AF:
0.000576
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00187
Gnomad4 FIN
AF:
0.000378
Gnomad4 NFE
AF:
0.00525
Gnomad4 OTH
AF:
0.00521
Alfa
AF:
0.00502
Hom.:
4
Bravo
AF:
0.00334
TwinsUK
AF:
0.00593
AC:
22
ALSPAC
AF:
0.00363
AC:
14
ESP6500AA
AF:
0.000681
AC:
3
ESP6500EA
AF:
0.00453
AC:
39
ExAC
AF:
0.00313
AC:
380
Asia WGS
AF:
0.00144
AC:
5
AN:
3478
EpiCase
AF:
0.00643
EpiControl
AF:
0.00533

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenJun 01, 2024MAP4: BS2 -
MAP4-related disorder Benign:1
Likely benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesMar 16, 2022This variant is classified as likely 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
Pathogenic
0.81
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Uncertain
0.050
CADD
Pathogenic
31
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.74
.;D;D;.;.
Eigen
Uncertain
0.62
Eigen_PC
Uncertain
0.60
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.97
D;D;D;D;D
M_CAP
Pathogenic
0.30
D
MetaRNN
Benign
0.011
T;T;T;T;T
MetaSVM
Uncertain
0.34
D
MutationAssessor
Benign
1.7
L;.;L;.;.
MutationTaster
Benign
1.0
D;N;N;N;N;N;N
PrimateAI
Uncertain
0.64
T
PROVEAN
Uncertain
-4.4
D;D;D;D;D
REVEL
Pathogenic
0.67
Sift
Pathogenic
0.0
D;D;D;D;D
Sift4G
Pathogenic
0.0010
D;D;D;D;D
Polyphen
1.0
D;D;D;D;.
Vest4
0.48
MVP
0.62
MPC
0.52
ClinPred
0.039
T
GERP RS
4.3
Varity_R
0.49
gMVP
0.63

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: rs150907099; hg19: chr3-47908815; COSMIC: COSV99275790; COSMIC: COSV99275790; API