5-67090227-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001164664.2(MAST4):​c.829C>T​(p.Arg277Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000869 in 1,611,430 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

MAST4
NM_001164664.2 missense

Scores

8
8
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.18
Variant links:
Genes affected
MAST4 (HGNC:19037): (microtubule associated serine/threonine kinase family member 4) This gene encodes a member of the microtubule-associated serine/threonine protein kinases. The proteins in this family contain a domain that gives the kinase the ability to determine its own scaffold to control the effects of their kinase activities. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2014]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.766

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MAST4NM_001164664.2 linkc.829C>T p.Arg277Trp missense_variant Exon 6 of 29 ENST00000403625.7 NP_001158136.1 O15021-5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MAST4ENST00000403625.7 linkc.829C>T p.Arg277Trp missense_variant Exon 6 of 29 5 NM_001164664.2 ENSP00000385727.1 O15021-5

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
151990
Hom.:
0
Cov.:
31
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:
0.000208
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000121
AC:
3
AN:
248128
Hom.:
0
AF XY:
0.0000149
AC XY:
2
AN XY:
134550
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000331
Gnomad FIN exome
AF:
0.0000465
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000166
GnomAD4 exome
AF:
0.00000891
AC:
13
AN:
1459440
Hom.:
0
Cov.:
30
AF XY:
0.00000826
AC XY:
6
AN XY:
726092
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000233
Gnomad4 FIN exome
AF:
0.0000188
Gnomad4 NFE exome
AF:
0.00000811
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
151990
Hom.:
0
Cov.:
31
AF XY:
0.0000135
AC XY:
1
AN XY:
74236
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:
0.000208
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 25, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.262C>T (p.R88W) alteration is located in exon 5 (coding exon 5) of the MAST4 gene. This alteration results from a C to T substitution at nucleotide position 262, causing the arginine (R) at amino acid position 88 to be replaced by a tryptophan (W). 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
0.98
BayesDel_addAF
Uncertain
0.14
D
BayesDel_noAF
Uncertain
0.070
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.098
T;.;.;.;.;T
Eigen
Uncertain
0.46
Eigen_PC
Uncertain
0.37
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Pathogenic
0.98
D;D;D;D;D;D
M_CAP
Uncertain
0.25
D
MetaRNN
Pathogenic
0.75
D;D;D;D;D;D
MetaSVM
Benign
-0.31
T
MutationAssessor
Uncertain
2.1
M;.;.;.;.;.
PrimateAI
Pathogenic
0.90
D
PROVEAN
Pathogenic
-7.0
D;D;D;D;D;D
REVEL
Uncertain
0.41
Sift
Pathogenic
0.0
D;D;D;D;D;D
Sift4G
Pathogenic
0.0010
D;D;D;D;D;D
Polyphen
1.0
D;D;D;.;D;.
Vest4
0.74
MVP
0.80
MPC
1.5
ClinPred
0.94
D
GERP RS
2.8
Varity_R
0.70
gMVP
0.60

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: rs1271570925; hg19: chr5-66386055; API