11-75608158-C-T

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

Scores

3
5
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.83
Variant links:
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]

Genome browser will be placed here

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
MAP6NM_033063.2 linkc.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
MAP6ENST00000304771.8 linkc.1070G>A p.Arg357His missense_variant 2/41 NM_033063.2 ENSP00000307093.3 Q96JE9-1
MAP6ENST00000434603.2 linkc.1070G>A p.Arg357His missense_variant 2/31 ENSP00000415108.2 Q96JE9-2
MAP6ENST00000526740.3 linkc.83G>A p.Arg28His missense_variant 2/45 ENSP00000434278.1 Q96JE9-3

Frequencies

GnomAD3 genomes
AF:
0.0000657
AC:
10
AN:
152168
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000577
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000735
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000115
AC:
29
AN:
251484
Hom.:
0
AF XY:
0.000103
AC XY:
14
AN XY:
135920
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.0000867
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.000185
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.000102
AC:
149
AN:
1461876
Hom.:
0
Cov.:
31
AF XY:
0.0000935
AC XY:
68
AN XY:
727238
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000671
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000756
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.0000749
Gnomad4 NFE exome
AF:
0.000117
Gnomad4 OTH exome
AF:
0.000116
GnomAD4 genome
AF:
0.0000657
AC:
10
AN:
152168
Hom.:
0
Cov.:
33
AF XY:
0.0000404
AC XY:
3
AN XY:
74334
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000577
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.0000718
ExAC
AF:
0.000173
AC:
21
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.000109
EpiControl
AF:
0.0000593

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 submitterclinical testingAmbry GeneticsSep 08, 2024The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.17
BayesDel_addAF
Benign
-0.056
T
BayesDel_noAF
Uncertain
-0.040
CADD
Pathogenic
30
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.32
T;.;.
Eigen
Pathogenic
0.76
Eigen_PC
Pathogenic
0.76
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.93
D;D;D
M_CAP
Benign
0.018
T
MetaRNN
Benign
0.38
T;T;T
MetaSVM
Benign
-0.43
T
MutationAssessor
Uncertain
2.2
M;.;M
PrimateAI
Benign
0.47
T
PROVEAN
Uncertain
-2.6
D;D;D
REVEL
Benign
0.28
Sift
Benign
0.077
T;D;T
Sift4G
Benign
0.076
T;D;T
Polyphen
1.0
D;.;.
Vest4
0.75
MutPred
0.69
Gain of ubiquitination at K353 (P = 0.0267);.;Gain of ubiquitination at K353 (P = 0.0267);
MVP
0.72
MPC
0.38
ClinPred
0.23
T
GERP RS
5.7
Varity_R
0.18
gMVP
0.32

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: rs750383326; hg19: chr11-75319203; COSMIC: COSV59074208; API