19-18122750-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP5_Moderate

The NM_001393504.1(MAST3):​c.398C>T​(p.Ser133Leu) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (★).

Frequency

Genomes: not found (cov: 33)

Consequence

MAST3
NM_001393504.1 missense, splice_region

Scores

5
10
4
Splicing: ADA: 0.9897
2

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 7.43
Variant links:
Genes affected
MAST3 (HGNC:19036): (microtubule associated serine/threonine kinase 3) Predicted to enable protein serine/threonine kinase activity. Predicted to be involved in cytoskeleton organization; intracellular signal transduction; and peptidyl-serine phosphorylation. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 19-18122750-C-T is Pathogenic according to our data. Variant chr19-18122750-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 3342723.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MAST3NM_001393504.1 linkc.398C>T p.Ser133Leu missense_variant, splice_region_variant Exon 6 of 28 ENST00000687212.1 NP_001380433.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MAST3ENST00000687212.1 linkc.398C>T p.Ser133Leu missense_variant, splice_region_variant Exon 6 of 28 NM_001393504.1 ENSP00000509890.1 A0A8I5KST9

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

ClinVar

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

Submissions by phenotype

not provided Pathogenic:1
Jun 21, 2023
GeneDx
Significance: Pathogenic
Review Status: criteria provided, single submitter
Collection Method: clinical testing

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; In silico analysis is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; This variant is associated with the following publications: (PMID: 35095415) -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.40
BayesDel_addAF
Uncertain
0.038
T
BayesDel_noAF
Benign
-0.18
CADD
Pathogenic
31
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.16
T
Eigen
Pathogenic
0.82
Eigen_PC
Pathogenic
0.76
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.97
D
M_CAP
Uncertain
0.20
D
MetaRNN
Uncertain
0.73
D
MetaSVM
Benign
-0.36
T
MutationAssessor
Uncertain
2.4
M
PrimateAI
Uncertain
0.71
T
PROVEAN
Pathogenic
-5.1
D
REVEL
Uncertain
0.48
Sift
Uncertain
0.016
D
Sift4G
Uncertain
0.019
D
Polyphen
0.99
D
Vest4
0.59
MutPred
0.57
Loss of phosphorylation at S104 (P = 0.0048);
MVP
0.60
MPC
0.94
ClinPred
0.98
D
GERP RS
5.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.46
gMVP
0.68

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
0.99
dbscSNV1_RF
Pathogenic
0.77
SpliceAI score (max)
0.32
Details are displayed if max score is > 0.2
DS_DL_spliceai
0.32
Position offset: 1

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: chr19-18233560; COSMIC: COSV53217754; COSMIC: COSV53217754; API