11-75608158-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_033063.2(MAP6):c.1070G>A(p.Arg357His) variant causes a missense change. The variant allele was found at a frequency of 0.0000985 in 1,614,044 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00010 ( 0 hom. )
Consequence
MAP6
NM_033063.2 missense
NM_033063.2 missense
Scores
3
5
11
Clinical Significance
Conservation
PhyloP100: 5.83
Genes affected
MAP6 (HGNC:6868): (microtubule associated protein 6) This gene encodes a microtubule-associated protein. The encoded protein is a calmodulin-binding and calmodulin-regulated protein that is involved in microtubule stabilization. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.37534484).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MAP6 | NM_033063.2 | c.1070G>A | p.Arg357His | missense_variant | 2/4 | ENST00000304771.8 | NP_149052.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MAP6 | ENST00000304771.8 | c.1070G>A | p.Arg357His | missense_variant | 2/4 | 1 | NM_033063.2 | ENSP00000307093.3 | ||
MAP6 | ENST00000434603.2 | c.1070G>A | p.Arg357His | missense_variant | 2/3 | 1 | ENSP00000415108.2 | |||
MAP6 | ENST00000526740.3 | c.83G>A | p.Arg28His | missense_variant | 2/4 | 5 | ENSP00000434278.1 |
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152168Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000115 AC: 29AN: 251484Hom.: 0 AF XY: 0.000103 AC XY: 14AN XY: 135920
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GnomAD4 exome AF: 0.000102 AC: 149AN: 1461876Hom.: 0 Cov.: 31 AF XY: 0.0000935 AC XY: 68AN XY: 727238
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GnomAD4 genome AF: 0.0000657 AC: 10AN: 152168Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3AN XY: 74334
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 08, 2024 | The c.1070G>A (p.R357H) alteration is located in exon 2 (coding exon 2) of the MAP6 gene. This alteration results from a G to A substitution at nucleotide position 1070, causing the arginine (R) at amino acid position 357 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;M
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D;D
REVEL
Benign
Sift
Benign
T;D;T
Sift4G
Benign
T;D;T
Polyphen
D;.;.
Vest4
MutPred
Gain of ubiquitination at K353 (P = 0.0267);.;Gain of ubiquitination at K353 (P = 0.0267);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
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