Genetic Variant MAP1S:p.Ser14Gly (chr19-17719542-A-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_018174.6(MAP1S):c.40A>G(p.Ser14Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000079 in 151,856 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 (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000018 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MAP1S
NM_018174.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.366

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.052594215).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP1S	NM_018174.6 link	c.40A>G	p.Ser14Gly	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.40A>G	p.Ser14Gly	missense_variant	Exon 1 of 7	1	NM_018174.6	ENSP00000325313.3		Q66K74-1

Frequencies

GnomAD3 genomes

AF:

0.0000527

AC:

AN:

151736

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000183

AC:

AN:

1093944

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

516450

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22958

American (AMR)

AF:

0.00

AC:

AN:

8398

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14346

East Asian (EAS)

AF:

0.00

AC:

AN:

26480

South Asian (SAS)

AF:

0.00

AC:

AN:

19536

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35270

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3594

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

919592

Other (OTH)

AF:

0.0000457

AC:

AN:

43770

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:

0.0000790

AC:

AN:

151856

Hom.:

Cov.:

AF XY:

0.0000942

AC XY:

AN XY:

74272

show subpopulations

African (AFR)

AF:

0.000242

AC:

AN:

41370

American (AMR)

AF:

0.000131

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5128

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10552

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67938

Other (OTH)

AF:

0.00

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

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

Oct 24, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.40A>G (p.S14G) alteration is located in exon 1 (coding exon 1) of the MAP1S gene. This alteration results from a A to G substitution at nucleotide position 40, causing the serine (S) at amino acid position 14 to be replaced by a glycine (G). 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

0.11

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Benign

0.67

DEOGEN2

Benign

0.066

T;.;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.60

T;T;T

M_CAP

Benign

0.044

MetaRNN

Benign

0.053

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.40

N;.;.

PhyloP100

0.37

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.66

N;.;.

REVEL

Benign

0.012

Sift

Benign

0.85

T;.;.

Sift4G

Benign

0.35

T;T;D

Polyphen

0.0

B;.;.

Vest4

0.18

MVP

0.25

MPC

0.26

ClinPred

0.037

GERP RS

0.016

PromoterAI

-0.034

Neutral

(source)

Varity_R

0.091

gMVP

0.46

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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19-17719542-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over