Variant 19-17726417-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000324096.9(MAP1S):c.1033G>A(p.Ala345Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000127 in 1,419,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

MAP1S
ENST00000324096.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.133

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:

MAP1S (HGNC:):

MAP1S links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.060071826).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP1S	NM_018174.6 linkuse as main transcript	c.1033G>A	p.Ala345Thr	missense_variant	5/7	ENST00000324096.9	NP_060644.4	Q66K74-1
MAP1S	NM_001308363.2 linkuse as main transcript	c.955G>A	p.Ala319Thr	missense_variant	5/7		NP_001295292.1	Q66K74-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP1S	ENST00000324096.9 linkuse as main transcript	c.1033G>A	p.Ala345Thr	missense_variant	5/7	1	NM_018174.6	ENSP00000325313.3		Q66K74-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000581

AC:

AN:

172214

Hom.:

AF XY:

0.0000105

AC XY:

AN XY:

95300

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:

0.00

Gnomad NFE exome

AF:

0.0000136

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000127

AC:

AN:

1419840

Hom.:

Cov.:

AF XY:

0.0000114

AC XY:

AN XY:

704172

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000137

Gnomad4 OTH exome

AF:

0.0000507

GnomAD4 genome

Cov.:

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 26, 2022

The c.1033G>A (p.A345T) alteration is located in exon 5 (coding exon 5) of the MAP1S gene. This alteration results from a G to A substitution at nucleotide position 1033, causing the alanine (A) at amino acid position 345 to be replaced by a threonine (T). 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

0.070

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.47

DANN

Benign

0.28

DEOGEN2

Benign

0.066

T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.60

T;T

M_CAP

Benign

0.0040

MetaRNN

Benign

0.060

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-1.1

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.39

N;N

REVEL

Benign

0.0070

Sift

Benign

0.63

T;T

Sift4G

Benign

0.35

T;T

Polyphen

0.040

B;.

Vest4

0.11

MutPred

0.27

Gain of phosphorylation at A345 (P = 0.0478);.;

MVP

0.12

MPC

0.28

ClinPred

0.012

GERP RS

0.17

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.034

gMVP

0.59

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over