19-17719519-G-A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018174.6(MAP1S):​c.17G>A​(p.Gly6Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000458 in 1,245,724 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G6V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000048 ( 0 hom. )

Consequence

MAP1S
NM_018174.6 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.65

Publications

0 publications found
Variant links:
Genes affected
MAP1S (HGNC:15715): (microtubule associated protein 1S) Enables DNA binding activity and cytoskeletal protein binding activity. Involved in microtubule bundle formation; neuron projection morphogenesis; and regulation of chromatin disassembly. Located in several cellular components, including microtubule cytoskeleton; nuclear lumen; and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.0785695).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MAP1SNM_018174.6 linkc.17G>A p.Gly6Glu missense_variant Exon 1 of 7 ENST00000324096.9 NP_060644.4 Q66K74-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MAP1SENST00000324096.9 linkc.17G>A p.Gly6Glu missense_variant Exon 1 of 7 1 NM_018174.6 ENSP00000325313.3 Q66K74-1

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152126
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
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:
0.00
Gnomad OTH
AF:
0.000478
GnomAD4 exome
AF:
0.0000475
AC:
52
AN:
1093598
Hom.:
0
Cov.:
30
AF XY:
0.0000484
AC XY:
25
AN XY:
516378
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
22948
American (AMR)
AF:
0.00
AC:
0
AN:
8390
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
14342
East Asian (EAS)
AF:
0.00
AC:
0
AN:
26474
South Asian (SAS)
AF:
0.00
AC:
0
AN:
19532
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
34954
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
3536
European-Non Finnish (NFE)
AF:
0.0000544
AC:
50
AN:
919678
Other (OTH)
AF:
0.0000457
AC:
2
AN:
43744
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.455
Heterozygous variant carriers
0
4
8
11
15
19
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
4
8
12
16
20
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152126
Hom.:
0
Cov.:
33
AF XY:
0.0000404
AC XY:
3
AN XY:
74324
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41440
American (AMR)
AF:
0.000262
AC:
4
AN:
15274
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5186
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4828
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10590
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
68016
Other (OTH)
AF:
0.000478
AC:
1
AN:
2092
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.455
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.0000604

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.096
BayesDel_addAF
Benign
-0.35
T
BayesDel_noAF
Benign
-0.75
CADD
Benign
0.29
DANN
Benign
0.74
DEOGEN2
Benign
0.046
T;.;.
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.6
FATHMM_MKL
Benign
0.021
N
LIST_S2
Benign
0.49
T;T;T
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.079
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.55
N;.;.
PhyloP100
-2.7
PrimateAI
Uncertain
0.74
T
PROVEAN
Benign
-0.49
N;.;.
REVEL
Benign
0.016
Sift
Benign
0.16
T;.;.
Sift4G
Benign
0.074
T;D;D
Polyphen
0.0010
B;.;.
Vest4
0.087
MutPred
0.22
Gain of helix (P = 0.0078);Gain of helix (P = 0.0078);Gain of helix (P = 0.0078);
MVP
0.068
MPC
0.36
ClinPred
0.13
T
GERP RS
-4.7
PromoterAI
-0.081
Neutral
Varity_R
0.045
gMVP
0.31
Mutation Taster
=90/10
polymorphism

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

Other links and lift over

dbSNP: rs948979492; hg19: chr19-17830328; API