Variant 19-18144549-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBA1

The NM_001393504.1(MAST3):c.2668G>A(p.Gly890Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 1,609,598 control chromosomes in the GnomAD database, including 227,209 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.48 ( 18175 hom., cov: 33)

Exomes 𝑓: 0.53 ( 209034 hom. )

Consequence

MAST3
NM_001393504.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.25

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 links:

MAST3-AS1 (HGNC:):

MAST3-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), MAST3. . Gene score misZ 4.1363 (greater than the threshold 3.09). Trascript score misZ 3.5232 (greater than threshold 3.09). GenCC has associacion of gene with developmental and epileptic encephalopathy 108.

BP4

Computational evidence support a benign effect (MetaRNN=8.170261E-6).

BP6

Variant 19-18144549-G-A is Benign according to our data. Variant chr19-18144549-G-A is described in ClinVar as [Benign]. Clinvar id is 1526372.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.669 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAST3	NM_001393504.1 linkuse as main transcript	c.2668G>A	p.Gly890Ser	missense_variant	23/28	ENST00000687212.1	NP_001380433.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAST3	ENST00000687212.1 linkuse as main transcript	c.2668G>A	p.Gly890Ser	missense_variant	23/28		NM_001393504.1	ENSP00000509890.1		A0A8I5KST9

Frequencies

GnomAD3 genomes

AF:

0.480

AC:

73011

AN:

151998

Hom.:

18177

Cov.:

show subpopulations

Gnomad AFR

AF:

0.349

Gnomad AMI

AF:

0.722

Gnomad AMR

AF:

0.494

Gnomad ASJ

AF:

0.476

Gnomad EAS

AF:

0.688

Gnomad SAS

AF:

0.648

Gnomad FIN

AF:

0.503

Gnomad MID

AF:

0.503

Gnomad NFE

AF:

0.523

Gnomad OTH

AF:

0.471

GnomAD3 exomes

AF:

0.535

AC:

129059

AN:

241430

Hom.:

35486

AF XY:

0.540

AC XY:

71176

AN XY:

131890

show subpopulations

Gnomad AFR exome

AF:

0.341

Gnomad AMR exome

AF:

0.516

Gnomad ASJ exome

AF:

0.446

Gnomad EAS exome

AF:

0.691

Gnomad SAS exome

AF:

0.644

Gnomad FIN exome

AF:

0.505

Gnomad NFE exome

AF:

0.525

Gnomad OTH exome

AF:

0.516

GnomAD4 exome

AF:

0.532

AC:

775892

AN:

1457482

Hom.:

209034

Cov.:

AF XY:

0.535

AC XY:

387975

AN XY:

725148

show subpopulations

Gnomad4 AFR exome

AF:

0.334

Gnomad4 AMR exome

AF:

0.512

Gnomad4 ASJ exome

AF:

0.454

Gnomad4 EAS exome

AF:

0.701

Gnomad4 SAS exome

AF:

0.640

Gnomad4 FIN exome

AF:

0.503

Gnomad4 NFE exome

AF:

0.529

Gnomad4 OTH exome

AF:

0.520

GnomAD4 genome

AF:

0.480

AC:

73027

AN:

152116

Hom.:

18175

Cov.:

AF XY:

0.481

AC XY:

35736

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.348

Gnomad4 AMR

AF:

0.494

Gnomad4 ASJ

AF:

0.476

Gnomad4 EAS

AF:

0.688

Gnomad4 SAS

AF:

0.648

Gnomad4 FIN

AF:

0.503

Gnomad4 NFE

AF:

0.523

Gnomad4 OTH

AF:

0.475

Alfa

AF:

0.513

Hom.:

39713

Bravo

AF:

0.470

TwinsUK

AF:

0.529

AC:

1960

ALSPAC

AF:

0.519

AC:

1999

ESP6500AA

AF:

0.342

AC:

1317

ESP6500EA

AF:

0.521

AC:

4297

ExAC

AF:

0.534

AC:

64279

Asia WGS

AF:

0.635

AC:

2209

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 22, 2022	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.011

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.78

MetaRNN

Benign

0.0000082

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.5

PrimateAI

Uncertain

0.50

PROVEAN

Benign

0.28

REVEL

Benign

0.15

Sift

Benign

0.34

Sift4G

Benign

0.67

Polyphen

0.0020

Vest4

0.020

MPC

0.74

ClinPred

0.0047

GERP RS

2.3

Varity_R

0.059

gMVP

0.27

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over