Genetic Variant MAST3:p.Ile565Ile (chr19-18134702-C-T) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001393504.1(MAST3):c.1695C>T(p.Ile565Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 1,612,518 control chromosomes in the GnomAD database, including 228,970 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.48 ( 18230 hom., cov: 31)

Exomes 𝑓: 0.53 ( 210740 hom. )

Consequence

MAST3
NM_001393504.1 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.730

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 19-18134702-C-T is Benign according to our data. Variant chr19-18134702-C-T is described in ClinVar as [Benign]. Clinvar id is 1179690.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.73 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAST3	NM_001393504.1 link	c.1695C>T	p.Ile565Ile	synonymous_variant	Exon 16 of 28	ENST00000687212.1	NP_001380433.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAST3	ENST00000687212.1 link	c.1695C>T	p.Ile565Ile	synonymous_variant	Exon 16 of 28		NM_001393504.1	ENSP00000509890.1		A0A8I5KST9

Frequencies

GnomAD3 genomes

AF:

0.481

AC:

73132

AN:

151906

Hom.:

18231

Cov.:

show subpopulations

Gnomad AFR

AF:

0.349

Gnomad AMI

AF:

0.723

Gnomad AMR

AF:

0.495

Gnomad ASJ

AF:

0.476

Gnomad EAS

AF:

0.684

Gnomad SAS

AF:

0.647

Gnomad FIN

AF:

0.505

Gnomad MID

AF:

0.503

Gnomad NFE

AF:

0.526

Gnomad OTH

AF:

0.472

GnomAD3 exomes

AF:

0.534

AC:

131943

AN:

246996

Hom.:

36188

AF XY:

0.540

AC XY:

72367

AN XY:

134082

show subpopulations

Gnomad AFR exome

AF:

0.341

Gnomad AMR exome

AF:

0.516

Gnomad ASJ exome

AF:

0.447

Gnomad EAS exome

AF:

0.686

Gnomad SAS exome

AF:

0.644

Gnomad FIN exome

AF:

0.506

Gnomad NFE exome

AF:

0.526

Gnomad OTH exome

AF:

0.517

GnomAD4 exome

AF:

0.534

AC:

780142

AN:

1460494

Hom.:

210740

Cov.:

AF XY:

0.537

AC XY:

389921

AN XY:

726440

show subpopulations

Gnomad4 AFR exome

AF:

0.334

Gnomad4 AMR exome

AF:

0.513

Gnomad4 ASJ exome

AF:

0.454

Gnomad4 EAS exome

AF:

0.698

Gnomad4 SAS exome

AF:

0.639

Gnomad4 FIN exome

AF:

0.505

Gnomad4 NFE exome

AF:

0.532

Gnomad4 OTH exome

AF:

0.522

GnomAD4 genome

AF:

0.481

AC:

73150

AN:

152024

Hom.:

18230

Cov.:

AF XY:

0.482

AC XY:

35784

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.348

Gnomad4 AMR

AF:

0.495

Gnomad4 ASJ

AF:

0.476

Gnomad4 EAS

AF:

0.684

Gnomad4 SAS

AF:

0.646

Gnomad4 FIN

AF:

0.505

Gnomad4 NFE

AF:

0.526

Gnomad4 OTH

AF:

0.476

Alfa

AF:

0.497

Hom.:

23829

Bravo

AF:

0.471

Asia WGS

AF:

0.631

AC:

2193

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

Jan 18, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

7.3

DANN

Benign

0.67

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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.

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