Genetic Variant MAP1S:p.Ala10Pro (chr19-17719530-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_018174.6(MAP1S):c.28G>C(p.Ala10Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000183 in 1,093,790 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. 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. A10D) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000018 ( 0 hom. )

Consequence

MAP1S
NM_018174.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.440

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]

MAP1S links:

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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=0.15371397).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP1S	NM_018174.6 link	c.28G>C	p.Ala10Pro	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
MAP1S	ENST00000324096.9 link	c.28G>C	p.Ala10Pro	missense_variant	Exon 1 of 7	1	NM_018174.6	ENSP00000325313.3		Q66K74-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000183

AC:

AN:

1093790

Hom.:

Cov.:

AF XY:

0.00000387

AC XY:

AN XY:

516444

show subpopulations

African (AFR)

AF:

0.0000436

AC:

AN:

22952

American (AMR)

AF:

0.00

AC:

AN:

8392

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14342

East Asian (EAS)

AF:

0.00

AC:

AN:

26474

South Asian (SAS)

AF:

0.00

AC:

AN:

19532

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35130

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3608

European-Non Finnish (NFE)

AF:

0.00000109

AC:

AN:

919602

Other (OTH)

AF:

0.00

AC:

AN:

43758

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 23, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.28G>C (p.A10P) alteration is located in exon 1 (coding exon 1) of the MAP1S gene. This alteration results from a G to C substitution at nucleotide position 28, causing the alanine (A) at amino acid position 10 to be replaced by a proline (P). 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

0.091

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Benign

0.80

DEOGEN2

Benign

0.052

T;.;.

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.072

LIST_S2

Benign

0.52

T;T;T

M_CAP

Benign

0.044

MetaRNN

Benign

0.15

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

L;.;.

PhyloP100

0.44

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.58

N;.;.

REVEL

Benign

0.12

Sift

Benign

0.17

T;.;.

Sift4G

Benign

0.13

T;T;T

Polyphen

0.99

D;.;.

Vest4

0.22

MutPred

0.29

Gain of relative solvent accessibility (P = 0.0023);Gain of relative solvent accessibility (P = 0.0023);Gain of relative solvent accessibility (P = 0.0023);

MVP

0.29

MPC

0.36

ClinPred

0.11

GERP RS

2.6

PromoterAI

-0.13

Neutral

(source)

Varity_R

0.071

gMVP

0.23

Mutation Taster

=93/7

polymorphism

(source)

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

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19-17719530-G-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over