6-136361126-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_003980.6(MAP7):​c.1580G>A​(p.Arg527His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000757 in 1,453,274 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R527G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000076 ( 0 hom. )

Consequence

MAP7
NM_003980.6 missense

Scores

1
6
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.56
Variant links:
Genes affected
MAP7 (HGNC:6869): (microtubule associated protein 7) The product of this gene is a microtubule-associated protein that is predominantly expressed in cells of epithelial origin. Microtubule-associated proteins are thought to be involved in microtubule dynamics, which is essential for cell polarization and differentiation. This protein has been shown to be able to stabilize microtubules, and may serve to modulate microtubule functions. Studies of the related mouse protein also suggested an essential role in microtubule function required for spermatogenesis. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2010]

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=0.26569754).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MAP7NM_003980.6 linkc.1580G>A p.Arg527His missense_variant Exon 12 of 18 ENST00000354570.8 NP_003971.1 Q14244-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MAP7ENST00000354570.8 linkc.1580G>A p.Arg527His missense_variant Exon 12 of 18 1 NM_003980.6 ENSP00000346581.2 Q14244-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000827
AC:
2
AN:
241732
Hom.:
0
AF XY:
0.0000151
AC XY:
2
AN XY:
132374
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000291
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000893
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000757
AC:
11
AN:
1453274
Hom.:
0
Cov.:
35
AF XY:
0.0000111
AC XY:
8
AN XY:
723386
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000899
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Oct 09, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1670G>A (p.R557H) alteration is located in exon 12 (coding exon 12) of the MAP7 gene. This alteration results from a G to A substitution at nucleotide position 1670, causing the arginine (R) at amino acid position 557 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
0.22
BayesDel_addAF
Benign
-0.051
T
BayesDel_noAF
Benign
-0.31
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.14
T;.;.;.;T;.;.;.;.
Eigen
Uncertain
0.21
Eigen_PC
Benign
0.048
FATHMM_MKL
Benign
0.29
N
LIST_S2
Uncertain
0.90
D;D;D;D;D;D;D;D;.
M_CAP
Benign
0.019
T
MetaRNN
Benign
0.27
T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Pathogenic
3.3
.;.;.;.;M;.;.;.;.
PrimateAI
Benign
0.46
T
PROVEAN
Uncertain
-2.4
.;N;.;.;D;D;D;D;.
REVEL
Benign
0.12
Sift
Uncertain
0.0020
.;D;.;.;D;D;D;D;.
Sift4G
Uncertain
0.0050
D;D;D;D;D;D;D;D;D
Polyphen
1.0, 1.0
.;.;.;D;D;.;.;.;.
Vest4
0.43
MutPred
0.34
.;.;.;.;Loss of MoRF binding (P = 0.0566);.;.;.;.;
MVP
0.25
MPC
0.19
ClinPred
0.87
D
GERP RS
5.8
Varity_R
0.39
gMVP
0.054

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: rs1301059510; hg19: chr6-136682264; API