chr19-18123582-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2

The NM_001393504.1(MAST3):​c.560C>T​(p.Pro187Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000825 in 1,575,092 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000077 ( 0 hom. )

Consequence

MAST3
NM_001393504.1 missense, splice_region

Scores

3
12
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.24
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 Likely_benign. Variant got -3 ACMG points.

PP3
MetaRNN computational evidence supports a deleterious effect, 0.777
BS2
High AC in GnomAdExome4 at 11 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MAST3NM_001393504.1 linkc.560C>T p.Pro187Leu missense_variant, splice_region_variant Exon 8 of 28 ENST00000687212.1 NP_001380433.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MAST3ENST00000687212.1 linkc.560C>T p.Pro187Leu missense_variant, splice_region_variant Exon 8 of 28 NM_001393504.1 ENSP00000509890.1 A0A8I5KST9

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152202
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000145
AC:
3
AN:
206876
Hom.:
0
AF XY:
0.0000268
AC XY:
3
AN XY:
111888
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000345
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000214
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000773
AC:
11
AN:
1422890
Hom.:
0
Cov.:
31
AF XY:
0.00000994
AC XY:
7
AN XY:
704438
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000255
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:
0.00000824
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152202
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74356
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000451
Hom.:
0
Bravo
AF:
0.0000113
ExAC
AF:
0.0000166
AC:
2

ClinVar

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

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Jun 28, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.473C>T (p.P158L) alteration is located in exon 7 (coding exon 7) of the MAST3 gene. This alteration results from a C to T substitution at nucleotide position 473, causing the proline (P) at amino acid position 158 to be replaced by a leucine (L). 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
Pathogenic
0.72
BayesDel_addAF
Benign
-0.022
T
BayesDel_noAF
Benign
-0.27
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.17
T
Eigen
Uncertain
0.63
Eigen_PC
Uncertain
0.49
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.94
D
M_CAP
Uncertain
0.27
D
MetaRNN
Pathogenic
0.78
D
MetaSVM
Uncertain
-0.12
T
MutationAssessor
Uncertain
2.8
M
PrimateAI
Uncertain
0.79
T
PROVEAN
Pathogenic
-9.2
D
REVEL
Uncertain
0.37
Sift
Uncertain
0.015
D
Sift4G
Uncertain
0.022
D
Polyphen
1.0
D
Vest4
0.21
MutPred
0.88
Gain of MoRF binding (P = 0.054);
MVP
0.68
MPC
2.1
ClinPred
1.0
D
GERP RS
4.7
Varity_R
0.44
gMVP
0.62

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: rs56059221; hg19: chr19-18234392; COSMIC: COSV53226221; API