Genetic Variant NM_018174.6:c.95A>T (chr19-17719597-A-T) – 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.95A>T(p.Tyr32Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000563 in 1,243,618 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., 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: 0.189

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=0.10765174).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP1S	NM_018174.6 link	c.95A>T	p.Tyr32Phe	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.95A>T	p.Tyr32Phe	missense_variant	Exon 1 of 7	1	NM_018174.6	ENSP00000325313.3		Q66K74-1

Frequencies

GnomAD3 genomes

AF:

0.0000330

AC:

AN:

151614

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

GnomAD4 exome

AF:

0.00000183

AC:

AN:

1091892

Hom.:

Cov.:

AF XY:

0.00000194

AC XY:

AN XY:

515430

show subpopulations

African (AFR)

AF:

0.0000875

AC:

AN:

22858

American (AMR)

AF:

0.00

AC:

AN:

8352

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14244

East Asian (EAS)

AF:

0.00

AC:

AN:

26366

South Asian (SAS)

AF:

0.00

AC:

AN:

19512

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35254

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3304

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

918404

Other (OTH)

AF:

0.00

AC:

AN:

43598

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

AF:

0.0000330

AC:

AN:

151726

Hom.:

Cov.:

AF XY:

0.0000405

AC XY:

AN XY:

74164

show subpopulations

African (AFR)

AF:

0.000121

AC:

AN:

41418

American (AMR)

AF:

0.00

AC:

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5146

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10440

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67878

Other (OTH)

AF:

0.00

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.435

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000491

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 28, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.95A>T (p.Y32F) alteration is located in exon 1 (coding exon 1) of the MAP1S gene. This alteration results from a A to T substitution at nucleotide position 95, causing the tyrosine (Y) at amino acid position 32 to be replaced by a phenylalanine (F). 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

0.12

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.13

T;.;.

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.73

T;T;T

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.11

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

L;.;.

PhyloP100

0.19

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.73

N;.;.

REVEL

Benign

0.027

Sift

Benign

0.68

T;.;.

Sift4G

Benign

0.70

T;T;T

Polyphen

0.60

P;.;.

Vest4

0.22

MVP

0.26

MPC

0.92

ClinPred

0.13

GERP RS

-0.15

PromoterAI

-0.097

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.11

gMVP

0.21

Mutation Taster

=95/5

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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NM_018174.6:c.95A>T

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