3-47867325-G-A
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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
NM_001385682.1 missense
Scores
5
10
4
Clinical Significance
Conservation
PhyloP100: 4.19
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 |
---|---|---|---|---|---|---|---|---|
MAP4 | NM_001385682.1 | c.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 |
---|---|---|---|---|---|---|---|---|---|---|
MAP4 | ENST00000683076.1 | c.6422C>T | p.Ser2141Phe | missense_variant | 17/21 | NM_001385682.1 | ENSP00000507895 | A2 |
Frequencies
GnomAD3 genomes AF: 0.00345 AC: 524AN: 152100Hom.: 2 Cov.: 32
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GnomAD3 exomes AF: 0.00311 AC: 780AN: 251178Hom.: 4 AF XY: 0.00328 AC XY: 445AN XY: 135758
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GnomAD4 exome AF: 0.00447 AC: 6527AN: 1459578Hom.: 28 Cov.: 29 AF XY: 0.00453 AC XY: 3293AN XY: 726284
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GnomAD4 genome AF: 0.00344 AC: 523AN: 152218Hom.: 2 Cov.: 32 AF XY: 0.00355 AC XY: 264AN XY: 74412
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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 submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2024 | MAP4: BS2 - |
MAP4-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 16, 2022 | This 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
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
.;D;D;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Benign
L;.;L;.;.
MutationTaster
Benign
D;N;N;N;N;N;N
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D;D;D;D
Sift4G
Pathogenic
D;D;D;D;D
Polyphen
D;D;D;D;.
Vest4
MVP
MPC
0.52
ClinPred
T
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at