Genetic Variant MAST3:p.Leu12Pro (chr19-18097827-T-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001393504.1(MAST3):c.35T>C(p.Leu12Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MAST3
NM_001393504.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.45

Publications

0 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 links:

IL12RB1 (HGNC:5971): (interleukin 12 receptor subunit beta 1) The protein encoded by this gene is a type I transmembrane protein that belongs to the hemopoietin receptor superfamily. This protein binds to interleukine 12 (IL12) with a low affinity, and is thought to be a part of IL12 receptor complex. This protein forms a disulfide-linked oligomer, which is required for its IL12 binding activity. The coexpression of this and IL12RB2 proteins was shown to lead to the formation of high-affinity IL12 binding sites and reconstitution of IL12 dependent signaling. Mutations in this gene impair the development of interleukin-17-producing T lymphocytes and result in increased susceptibility to mycobacterial and Salmonella infections. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

IL12RB1 Gene-Disease associations (from GenCC):

Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 deficiency
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

IL12RB1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.35T>C	p.Leu12Pro	missense	Exon 1 of 28	NP_001380433.1	A0A8I5KST9
MAST3	NM_001393501.1		c.35T>C	p.Leu12Pro	missense	Exon 1 of 29	NP_001380430.1
MAST3	NM_001393502.1		c.35T>C	p.Leu12Pro	missense	Exon 1 of 28	NP_001380431.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAST3	ENST00000687212.1	MANE Select	c.35T>C	p.Leu12Pro	missense	Exon 1 of 28	ENSP00000509890.1	A0A8I5KST9
MAST3	ENST00000262811.10	TSL:1	c.35T>C	p.Leu12Pro	missense	Exon 1 of 27	ENSP00000262811.4	O60307
IL12RB1	ENST00000600835.6	TSL:1	c.-110+928A>G		intron	N/A	ENSP00000470788.1	P42701-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1076908

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

508764

African (AFR)

AF:

0.00

AC:

AN:

22734

American (AMR)

AF:

0.00

AC:

AN:

8302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14160

East Asian (EAS)

AF:

0.00

AC:

AN:

26304

South Asian (SAS)

AF:

0.00

AC:

AN:

19652

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21074

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3008

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

918258

Other (OTH)

AF:

0.00

AC:

AN:

43416

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.020

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.013

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.78

M_CAP

Pathogenic

0.77

MetaRNN

Uncertain

0.73

MetaSVM

Uncertain

-0.27

MutationAssessor

Benign

1.7

PhyloP100

1.5

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.33

REVEL

Uncertain

0.37

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0040

Polyphen

0.99

Vest4

0.59

MutPred

0.19

Gain of loop (P = 0.0312)

MVP

0.85

MPC

1.8

ClinPred

0.89

GERP RS

4.5

PromoterAI

-0.0032

Neutral

(source)

Varity_R

0.40

gMVP

0.43

Mutation Taster

=86/14

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over