19-17725976-C-A

Variant summary

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

The NM_018174.6(MAP1S):​c.592C>A​(p.Pro198Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 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)

Consequence

MAP1S
NM_018174.6 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.05
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]

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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=0.20122859).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MAP1SNM_018174.6 linkc.592C>A p.Pro198Thr missense_variant Exon 5 of 7 ENST00000324096.9 NP_060644.4 Q66K74-1
MAP1SNM_001308363.2 linkc.514C>A p.Pro172Thr missense_variant Exon 5 of 7 NP_001295292.1 Q66K74-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MAP1SENST00000324096.9 linkc.592C>A p.Pro198Thr missense_variant Exon 5 of 7 1 NM_018174.6 ENSP00000325313.3 Q66K74-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 03, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.592C>A (p.P198T) alteration is located in exon 5 (coding exon 5) of the MAP1S gene. This alteration results from a C to A substitution at nucleotide position 592, causing the proline (P) at amino acid position 198 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
0.088
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.45
CADD
Benign
13
DANN
Uncertain
0.99
DEOGEN2
Benign
0.16
T;.;.
Eigen
Benign
-0.14
Eigen_PC
Benign
-0.34
FATHMM_MKL
Benign
0.030
N
LIST_S2
Benign
0.40
T;T;T
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.20
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.7
M;.;.
PrimateAI
Benign
0.40
T
PROVEAN
Benign
-2.2
N;.;N
REVEL
Benign
0.088
Sift
Benign
0.082
T;.;T
Sift4G
Benign
0.24
T;D;T
Polyphen
1.0
D;.;.
Vest4
0.19
MutPred
0.27
Loss of catalytic residue at P197 (P = 0.0365);.;.;
MVP
0.35
MPC
1.0
ClinPred
0.75
D
GERP RS
3.2
Varity_R
0.071
gMVP
0.49

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-17836785; API