6-136360746-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_003980.6(MAP7):​c.1754G>A​(p.Arg585Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000458 in 1,614,022 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000047 ( 0 hom. )

Consequence

MAP7
NM_003980.6 missense

Scores

3
11
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.63
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 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.772

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MAP7NM_003980.6 linkc.1754G>A p.Arg585Gln missense_variant Exon 13 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.1754G>A p.Arg585Gln missense_variant Exon 13 of 18 1 NM_003980.6 ENSP00000346581.2 Q14244-1

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152204
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000318
AC:
8
AN:
251456
Hom.:
0
AF XY:
0.0000294
AC XY:
4
AN XY:
135906
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000463
Gnomad NFE exome
AF:
0.0000527
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000472
AC:
69
AN:
1461818
Hom.:
0
Cov.:
31
AF XY:
0.0000385
AC XY:
28
AN XY:
727202
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.000150
Gnomad4 NFE exome
AF:
0.0000522
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152204
Hom.:
0
Cov.:
32
AF XY:
0.0000404
AC XY:
3
AN XY:
74344
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000102
Hom.:
0
Bravo
AF:
0.0000227
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000165
AC:
2

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Aug 12, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1844G>A (p.R615Q) alteration is located in exon 13 (coding exon 13) of the MAP7 gene. This alteration results from a G to A substitution at nucleotide position 1844, causing the arginine (R) at amino acid position 615 to be replaced by a glutamine (Q). 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
Uncertain
0.35
BayesDel_addAF
Uncertain
0.065
T
BayesDel_noAF
Uncertain
-0.010
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.34
T;.;.;.;T;.;.;.;.
Eigen
Uncertain
0.60
Eigen_PC
Uncertain
0.54
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.97
D;D;D;D;D;D;D;D;.
M_CAP
Benign
0.033
D
MetaRNN
Pathogenic
0.77
D;D;D;D;D;D;D;D;D
MetaSVM
Benign
-0.86
T
MutationAssessor
Uncertain
2.5
.;.;.;.;M;.;.;.;.
PrimateAI
Uncertain
0.66
T
PROVEAN
Uncertain
-3.4
.;D;.;.;D;D;D;D;.
REVEL
Benign
0.28
Sift
Pathogenic
0.0
.;D;.;.;D;D;D;D;.
Sift4G
Pathogenic
0.0
D;D;D;D;D;D;D;D;D
Polyphen
1.0, 1.0
.;.;.;D;D;.;.;.;.
Vest4
0.86
MVP
0.67
MPC
0.18
ClinPred
0.84
D
GERP RS
4.8
Varity_R
0.71
gMVP
0.17

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: rs372519059; hg19: chr6-136681884; COSMIC: COSV63416761; COSMIC: COSV63416761; API