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GeneBe

4-155352633-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001039580.2(MAP9):c.1784A>G(p.Lys595Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000045 in 1,555,564 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000043 ( 0 hom. )

Consequence

MAP9
NM_001039580.2 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.41
Variant links:
Genes affected
MAP9 (HGNC:26118): (microtubule associated protein 9) ASAP is a microtubule-associated protein required for spindle function, mitotic progression, and cytokinesis (Saffin et al., 2005 [PubMed 16049101]).[supplied by OMIM, Mar 2008]
MAP9-AS1 (HGNC:56110): (MAP9 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.1214768).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MAP9NM_001039580.2 linkuse as main transcriptc.1784A>G p.Lys595Arg missense_variant 13/14 ENST00000311277.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MAP9ENST00000311277.9 linkuse as main transcriptc.1784A>G p.Lys595Arg missense_variant 13/141 NM_001039580.2 P1Q49MG5-1
MAP9-AS1ENST00000630664.2 linkuse as main transcriptn.209-1576T>C intron_variant, non_coding_transcript_variant 5

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152018
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000216
AC:
5
AN:
231772
Hom.:
0
AF XY:
0.00000796
AC XY:
1
AN XY:
125690
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000237
Gnomad SAS exome
AF:
0.0000370
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000427
AC:
6
AN:
1403546
Hom.:
0
Cov.:
24
AF XY:
0.00000143
AC XY:
1
AN XY:
700374
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000102
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000343
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
152018
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74264
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000192
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113
ExAC
AF:
0.0000330
AC:
4

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 GeneticsJun 23, 2023The c.1784A>G (p.K595R) alteration is located in exon 13 (coding exon 12) of the MAP9 gene. This alteration results from a A to G substitution at nucleotide position 1784, causing the lysine (K) at amino acid position 595 to be replaced by an arginine (R). 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
0.097
BayesDel_addAF
Benign
-0.41
T
BayesDel_noAF
Benign
-0.54
Cadd
Benign
22
Dann
Uncertain
0.99
DEOGEN2
Benign
0.034
T;.
Eigen
Uncertain
0.51
Eigen_PC
Uncertain
0.50
FATHMM_MKL
Uncertain
0.84
D
LIST_S2
Benign
0.67
T;T
M_CAP
Benign
0.0067
T
MetaRNN
Benign
0.12
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.5
L;.
MutationTaster
Benign
0.87
D;D
PrimateAI
Benign
0.44
T
PROVEAN
Benign
-1.3
N;N
REVEL
Benign
0.049
Sift
Uncertain
0.026
D;D
Sift4G
Benign
0.23
T;T
Polyphen
0.97
D;.
Vest4
0.26
MutPred
0.15
Loss of methylation at K595 (P = 0.0099);.;
MVP
0.51
MPC
0.069
ClinPred
0.18
T
GERP RS
5.2
Varity_R
0.11
gMVP
0.036

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: rs768217783; hg19: chr4-156273785; API