dbSNP rs56059221: MAST3:p.Pro187Arg (chr19-18123582-C-G) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_001393504.1(MAST3):c.560C>G(p.Pro187Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. 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: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MAST3
NM_001393504.1 missense, splice_region

Scores

Clinical Significance

Not reported in ClinVar

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.788

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>G	p.Pro187Arg	missense splice_region	Exon 8 of 28	NP_001380433.1	A0A8I5KST9
MAST3	NM_001393501.1		c.584C>G	p.Pro195Arg	missense splice_region	Exon 9 of 29	NP_001380430.1
MAST3	NM_001393502.1		c.563C>G	p.Pro188Arg	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>G	p.Pro187Arg	missense splice_region	Exon 8 of 28	ENSP00000509890.1	A0A8I5KST9
MAST3	ENST00000262811.10	TSL:1	c.473C>G	p.Pro158Arg	missense splice_region	Exon 7 of 27	ENSP00000262811.4	O60307
MAST3	ENST00000697701.1		c.539C>G	p.Pro180Arg	missense splice_region	Exon 7 of 27	ENSP00000513408.1	A0A8V8TLL8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1422890

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

704438

African (AFR)

AF:

0.00

AC:

AN:

32554

American (AMR)

AF:

0.00

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:

0.00

AC:

AN:

5672

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1092662

Other (OTH)

AF:

0.00

AC:

AN:

58676

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.82

BayesDel_addAF

Benign

-0.037

BayesDel_noAF

Benign

-0.29

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

Pathogenic

0.98

M_CAP

Uncertain

0.17

MetaRNN

Pathogenic

0.79

MetaSVM

Uncertain

-0.12

MutationAssessor

Uncertain

2.8

PhyloP100

3.2

PrimateAI

Uncertain

0.78

PROVEAN

Pathogenic

-8.3

REVEL

Uncertain

0.39

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.46

MutPred

0.80

Gain of MoRF binding (P = 0.0075)

MVP

0.61

MPC

2.2

ClinPred

1.0

GERP RS

4.7

Varity_R

0.65

gMVP

0.62

Mutation Taster

=69/31

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over