19-18123582-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P187Q) has been classified 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

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 3.24

Publications

3 publications found

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 Gene-Disease associations (from GenCC):

developmental and epileptic encephalopathy 108
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

MAST3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.777

BS2

High AC in GnomAdExome4 at 11 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393504.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAST3	NM_001393504.1	MANE Select	c.560C>T	p.Pro187Leu	missense splice_region	Exon 8 of 28	NP_001380433.1	A0A8I5KST9
MAST3	NM_001393501.1		c.584C>T	p.Pro195Leu	missense splice_region	Exon 9 of 29	NP_001380430.1
MAST3	NM_001393502.1		c.563C>T	p.Pro188Leu	missense splice_region	Exon 8 of 28	NP_001380431.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAST3	ENST00000687212.1	MANE Select	c.560C>T	p.Pro187Leu	missense splice_region	Exon 8 of 28	ENSP00000509890.1	A0A8I5KST9
MAST3	ENST00000262811.10	TSL:1	c.473C>T	p.Pro158Leu	missense splice_region	Exon 7 of 27	ENSP00000262811.4	O60307
MAST3	ENST00000697701.1		c.539C>T	p.Pro180Leu	missense splice_region	Exon 7 of 27	ENSP00000513408.1	A0A8V8TLL8

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152202

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.0000145

AC:

AN:

206876

AF XY:

0.0000268

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000214

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000773

AC:

AN:

1422890

Hom.:

Cov.:

AF XY:

0.00000994

AC XY:

AN XY:

704438

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32554

American (AMR)

AF:

0.0000255

AC:

AN:

39242

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24062

East Asian (EAS)

AF:

0.00

AC:

AN:

39000

South Asian (SAS)

AF:

0.00

AC:

AN:

79426

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51596

Middle Eastern (MID)

AF:

0.000176

AC:

AN:

5672

European-Non Finnish (NFE)

AF:

0.00000824

AC:

AN:

1092662

Other (OTH)

AF:

0.00

AC:

AN:

58676

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41456

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000451

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000166

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.72

BayesDel_addAF

Benign

-0.022

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.94

M_CAP

Uncertain

0.27

MetaRNN

Pathogenic

0.78

MetaSVM

Uncertain

-0.12

MutationAssessor

Uncertain

2.8

PhyloP100

3.2

PrimateAI

Uncertain

0.79

PROVEAN

Pathogenic

-9.2

REVEL

Uncertain

0.37

Sift

Uncertain

0.015

Sift4G

Uncertain

0.022

Polyphen

1.0

Vest4

0.21

MutPred

0.88

Gain of MoRF binding (P = 0.054)

MVP

0.68

MPC

2.1

ClinPred

1.0

GERP RS

4.7

Varity_R

0.44

gMVP

0.62

Mutation Taster

=76/24

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over