Variant 19-12840512-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_014975.3(MAST1):c.150C>A(p.His50Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,606 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

MAST1
NM_014975.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.536

Variant links:

Genes affected

MAST1 (HGNC:19034): (microtubule associated serine/threonine kinase 1) This gene is a member of the microtubule-associated serine/threonine kinase (MAST) family. The protein encoded by this gene has an N-terminal serine/threonine kinase domain followed by a postsynaptic density protein-95/discs large/zona occludens-1 (PDZ) domain. In mouse and rat, the orthologous protein associates with the cytoskeleton and can bind both beta-2-syntrophin and neuronal nitric oxide synthase (nNOS) through its PDZ domain. In mouse and rat, this protein also co-localizes with dystrophin- and utrophin-associated protein complexes (DAPC/UAPC) in the vascular endothelium of the central nervous system. [provided by RefSeq, May 2017]

MAST1 links:

MAST1 (HGNC:):

MAST1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), MAST1. . Gene score misZ 5.7703 (greater than the threshold 3.09). Trascript score misZ 4.4543 (greater than threshold 3.09). GenCC has associacion of gene with mega-corpus-callosum syndrome with cerebellar hypoplasia and cortical malformations.

BP4

Computational evidence support a benign effect (MetaRNN=0.24080092).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAST1	NM_014975.3 linkuse as main transcript	c.150C>A	p.His50Gln	missense_variant	2/26	ENST00000251472.9	NP_055790.1	Q9Y2H9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MAST1	ENST00000251472.9 linkuse as main transcript	c.150C>A	p.His50Gln	missense_variant	2/26	1	NM_014975.3	ENSP00000251472.3	Q9Y2H9
MAST1	ENST00000591495.6 linkuse as main transcript	c.138C>A	p.His46Gln	missense_variant	3/13	5		ENSP00000466470.1	K7EME4
MAST1	ENST00000590883.1 linkuse as main transcript	n.250C>A		non_coding_transcript_exon_variant	2/6	5
HOOK2	ENST00000589765.1 linkuse as main transcript	n.33-14012G>T		intron_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461606

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727112

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 02, 2021

The c.150C>A (p.H50Q) alteration is located in exon 2 (coding exon 2) of the MAST1 gene. This alteration results from a C to A substitution at nucleotide position 150, causing the histidine (H) at amino acid position 50 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.85

BayesDel_addAF

Benign

-0.013

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.089

T;T

Eigen

Benign

0.0078

Eigen_PC

Benign

0.012

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.79

T;T

M_CAP

Benign

0.064

MetaRNN

Benign

0.24

T;T

MetaSVM

Benign

-0.42

MutationAssessor

Uncertain

2.2

.;M

PrimateAI

Uncertain

0.68

PROVEAN

Pathogenic

-6.6

.;D

REVEL

Uncertain

0.31

Sift

Benign

0.039

.;D

Sift4G

Benign

0.15

T;T

Polyphen

1.0

.;D

Vest4

0.35

MutPred

0.12

.;Loss of glycosylation at P49 (P = 0.1107);

MVP

0.84

ClinPred

0.95

GERP RS

2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.52

gMVP

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over