19-18123979-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBA1

The NM_001393504.1(MAST3):​c.674C>T​(p.Thr225Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0152 in 1,584,122 control chromosomes in the GnomAD database, including 495 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 85 hom., cov: 32)
Exomes 𝑓: 0.015 ( 410 hom. )

Consequence

MAST3
NM_001393504.1 missense

Scores

2
16

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.25
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 Benign. Variant got -19 ACMG points.

PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), MAST3. . Gene score misZ 4.1363 (greater than the threshold 3.09). Trascript score misZ 3.5232 (greater than threshold 3.09). GenCC has associacion of gene with developmental and epileptic encephalopathy 108.
BP4
Computational evidence support a benign effect (MetaRNN=0.0024982989).
BP6
Variant 19-18123979-C-T is Benign according to our data. Variant chr19-18123979-C-T is described in ClinVar as [Benign]. Clinvar id is 1235487.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0707 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MAST3NM_001393504.1 linkuse as main transcriptc.674C>T p.Thr225Met missense_variant 9/28 ENST00000687212.1 NP_001380433.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MAST3ENST00000687212.1 linkuse as main transcriptc.674C>T p.Thr225Met missense_variant 9/28 NM_001393504.1 ENSP00000509890.1 A0A8I5KST9

Frequencies

GnomAD3 genomes
AF:
0.0184
AC:
2794
AN:
152214
Hom.:
83
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00357
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0740
Gnomad ASJ
AF:
0.0277
Gnomad EAS
AF:
0.0414
Gnomad SAS
AF:
0.0548
Gnomad FIN
AF:
0.0113
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0114
Gnomad OTH
AF:
0.0210
GnomAD3 exomes
AF:
0.0306
AC:
6112
AN:
199496
Hom.:
198
AF XY:
0.0292
AC XY:
3180
AN XY:
109028
show subpopulations
Gnomad AFR exome
AF:
0.00266
Gnomad AMR exome
AF:
0.0926
Gnomad ASJ exome
AF:
0.0311
Gnomad EAS exome
AF:
0.0383
Gnomad SAS exome
AF:
0.0504
Gnomad FIN exome
AF:
0.0105
Gnomad NFE exome
AF:
0.00975
Gnomad OTH exome
AF:
0.0216
GnomAD4 exome
AF:
0.0149
AC:
21319
AN:
1431790
Hom.:
410
Cov.:
34
AF XY:
0.0158
AC XY:
11209
AN XY:
710282
show subpopulations
Gnomad4 AFR exome
AF:
0.00248
Gnomad4 AMR exome
AF:
0.0904
Gnomad4 ASJ exome
AF:
0.0298
Gnomad4 EAS exome
AF:
0.0266
Gnomad4 SAS exome
AF:
0.0490
Gnomad4 FIN exome
AF:
0.0115
Gnomad4 NFE exome
AF:
0.00915
Gnomad4 OTH exome
AF:
0.0177
GnomAD4 genome
AF:
0.0184
AC:
2805
AN:
152332
Hom.:
85
Cov.:
32
AF XY:
0.0204
AC XY:
1520
AN XY:
74496
show subpopulations
Gnomad4 AFR
AF:
0.00356
Gnomad4 AMR
AF:
0.0743
Gnomad4 ASJ
AF:
0.0277
Gnomad4 EAS
AF:
0.0413
Gnomad4 SAS
AF:
0.0551
Gnomad4 FIN
AF:
0.0113
Gnomad4 NFE
AF:
0.0114
Gnomad4 OTH
AF:
0.0227
Alfa
AF:
0.0132
Hom.:
35
Bravo
AF:
0.0212
TwinsUK
AF:
0.00944
AC:
35
ALSPAC
AF:
0.0106
AC:
41
ESP6500AA
AF:
0.00403
AC:
17
ESP6500EA
AF:
0.0113
AC:
96
ExAC
AF:
0.0228
AC:
2735
Asia WGS
AF:
0.0530
AC:
183
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxDec 20, 2020- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.083
BayesDel_addAF
Benign
-0.68
T
BayesDel_noAF
Benign
-0.67
CADD
Benign
18
DANN
Uncertain
1.0
DEOGEN2
Benign
0.16
T
Eigen
Benign
-0.53
Eigen_PC
Benign
-0.64
FATHMM_MKL
Benign
0.20
N
LIST_S2
Benign
0.52
T
MetaRNN
Benign
0.0025
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.8
L
PrimateAI
Benign
0.47
T
PROVEAN
Uncertain
-2.6
D
REVEL
Benign
0.068
Sift
Benign
0.076
T
Sift4G
Benign
0.10
T
Polyphen
0.51
P
Vest4
0.052
MPC
1.2
ClinPred
0.029
T
GERP RS
2.4
Varity_R
0.037
gMVP
0.13

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs56022120; hg19: chr19-18234789; API