Variant 19-17725906-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000324096.9(MAP1S):c.522C>G(p.Asp174Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,492 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: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

MAP1S
ENST00000324096.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0850

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13331404).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP1S	NM_018174.6 linkuse as main transcript	c.522C>G	p.Asp174Glu	missense_variant	5/7	ENST00000324096.9	NP_060644.4	Q66K74-1
MAP1S	NM_001308363.2 linkuse as main transcript	c.444C>G	p.Asp148Glu	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.522C>G	p.Asp174Glu	missense_variant	5/7	1	NM_018174.6	ENSP00000325313.3		Q66K74-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461492

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727060

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

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

May 11, 2022

The c.522C>G (p.D174E) alteration is located in exon 5 (coding exon 5) of the MAP1S gene. This alteration results from a C to G substitution at nucleotide position 522, causing the aspartic acid (D) at amino acid position 174 to be replaced by a glutamic acid (E). 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

0.17

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.032

T;T;.;.

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.0079

LIST_S2

Benign

0.57

T;T;T;T

M_CAP

Benign

0.0046

MetaRNN

Benign

0.13

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

.;L;.;.

MutationTaster

Benign

0.95

N;N

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.6

.;N;.;N

REVEL

Benign

0.0090

Sift

Benign

0.21

.;T;.;T

Sift4G

Benign

0.74

T;T;T;T

Polyphen

0.0020

.;B;.;.

Vest4

0.038, 0.026

MutPred

0.27

Loss of catalytic residue at G173 (P = 0.1486);Loss of catalytic residue at G173 (P = 0.1486);.;.;

MVP

0.14

MPC

0.40

ClinPred

0.025

GERP RS

2.0

Varity_R

0.027

gMVP

0.28

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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