19-18144558-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001393504.1(MAST3):​c.2677C>T​(p.Arg893Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000435 in 1,609,788 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

MAST3
NM_001393504.1 missense

Scores

1
10
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.55
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]
MAST3-AS1 (HGNC:55276): (MAST3 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.28391868).
BS2
High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MAST3NM_001393504.1 linkc.2677C>T p.Arg893Cys missense_variant Exon 23 of 28 ENST00000687212.1 NP_001380433.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MAST3ENST00000687212.1 linkc.2677C>T p.Arg893Cys missense_variant Exon 23 of 28 NM_001393504.1 ENSP00000509890.1 A0A8I5KST9

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152206
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000343
AC:
5
AN:
1457582
Hom.:
0
Cov.:
36
AF XY:
0.00000414
AC XY:
3
AN XY:
725248
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
0.00000360
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152206
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74346
show subpopulations
Gnomad4 AFR
AF:
0.0000241
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:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756

ClinVar

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

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Jan 26, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2590C>T (p.R864C) alteration is located in exon 22 (coding exon 22) of the MAST3 gene. This alteration results from a C to T substitution at nucleotide position 2590, causing the arginine (R) at amino acid position 864 to be replaced by a cysteine (C). 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
0.16
BayesDel_addAF
Uncertain
0.016
T
BayesDel_noAF
Benign
-0.21
CADD
Pathogenic
31
DANN
Uncertain
1.0
DEOGEN2
Benign
0.032
T
Eigen
Uncertain
0.39
Eigen_PC
Uncertain
0.41
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.92
D
M_CAP
Uncertain
0.091
D
MetaRNN
Benign
0.28
T
MetaSVM
Benign
-0.41
T
MutationAssessor
Uncertain
2.3
M
PrimateAI
Uncertain
0.61
T
PROVEAN
Benign
-2.0
N
REVEL
Benign
0.18
Sift
Uncertain
0.0080
D
Sift4G
Uncertain
0.026
D
Polyphen
0.98
D
Vest4
0.16
MutPred
0.27
Loss of MoRF binding (P = 0.0187);
MVP
0.52
MPC
1.7
ClinPred
0.99
D
GERP RS
4.6
Varity_R
0.21
gMVP
0.54

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: rs1159205899; hg19: chr19-18255368; COSMIC: COSV53222761; COSMIC: COSV53222761; API