Variant 19-12838566-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

The NM_014975.3(MAST1):c.-7C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000699 in 1,519,330 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0036 ( 1 hom., cov: 31)

Exomes 𝑓: 0.00037 ( 5 hom. )

Consequence

MAST1
NM_014975.3 5_prime_UTR

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.342

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:

HOOK2 (HGNC:19885): (hook microtubule tethering protein 2) Hook proteins are cytosolic coiled-coil proteins that contain conserved N-terminal domains, which attach to microtubules, and more divergent C-terminal domains, which mediate binding to organelles. The Drosophila Hook protein is a component of the endocytic compartment.[supplied by OMIM, Apr 2004]

HOOK2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.27).

BP6

Variant 19-12838566-C-A is Benign according to our data. Variant chr19-12838566-C-A is described in ClinVar as [Benign]. Clinvar id is 3048050.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 555 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAST1	NM_014975.3 link	c.-7C>A		5_prime_UTR_variant	Exon 1 of 26	ENST00000251472.9	NP_055790.1	Q9Y2H9

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MAST1	ENST00000251472 link	c.-7C>A	5_prime_UTR_variant	Exon 1 of 26	1	NM_014975.3	ENSP00000251472.3	Q9Y2H9
MAST1	ENST00000591495.6 link	c.71+266C>A	intron_variant	Intron 2 of 12	5		ENSP00000466470.1	K7EME4
MAST1	ENST00000590883.1 link	n.94C>A	non_coding_transcript_exon_variant	Exon 1 of 6	5
HOOK2	ENST00000589765.1 link	n.33-12066G>T	intron_variant	Intron 1 of 3	5

Frequencies

GnomAD3 genomes

AF:

0.00364

AC:

553

AN:

151990

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0123

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00183

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000948

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00104

AC:

201

AN:

193516

Hom.:

AF XY:

0.000735

AC XY:

AN XY:

107472

show subpopulations

Gnomad AFR exome

AF:

0.0146

Gnomad AMR exome

AF:

0.00103

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000101

Gnomad NFE exome

AF:

0.000167

Gnomad OTH exome

AF:

0.000706

GnomAD4 exome

AF:

0.000371

AC:

507

AN:

1367232

Hom.:

Cov.:

AF XY:

0.000312

AC XY:

212

AN XY:

680326

show subpopulations

Gnomad4 AFR exome

AF:

0.0110

Gnomad4 AMR exome

AF:

0.00111

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000133

Gnomad4 FIN exome

AF:

0.000123

Gnomad4 NFE exome

AF:

0.0000640

Gnomad4 OTH exome

AF:

0.00128

GnomAD4 genome

AF:

0.00365

AC:

555

AN:

152098

Hom.:

Cov.:

AF XY:

0.00320

AC XY:

238

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.0123

Gnomad4 AMR

AF:

0.00183

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000948

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00135

Hom.:

Bravo

AF:

0.00410

Asia WGS

AF:

0.000289

AC:

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MAST1-related disorder

Benign:1

Dec 09, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Benign

0.95

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

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