rs7919803

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001172303.3(MASTL):c.-28C>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 0.624 in 1,575,846 control chromosomes in the GnomAD database, including 309,884 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.60 ( 27801 hom., cov: 32)

Exomes 𝑓: 0.63 ( 282083 hom. )

Consequence

MASTL
NM_001172303.3 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.224

Variant links:

Genes affected

MASTL (HGNC:19042): (microtubule associated serine/threonine kinase like) This gene encodes a microtubule-associated serine/threonine kinase. Mutations at this locus have been associated with autosomal dominant thrombocytopenia, also known as thrombocytopenia-2. Alternatively spliced transcript variants have been described for this locus. [provided by RefSeq, Feb 2010]

MASTL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 10-27155399-C-A is Benign according to our data. Variant chr10-27155399-C-A is described in ClinVar as [Benign]. Clinvar id is 262113.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.643 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MASTL	NM_001172303.3 linkuse as main transcript	c.-28C>A		5_prime_UTR_variant	1/12	ENST00000375940.9

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MASTL	ENST00000375940.9 linkuse as main transcript	c.-28C>A	5_prime_UTR_variant	1/12	1	NM_001172303.3	P5	Q96GX5-1
MASTL	ENST00000375946.8 linkuse as main transcript	c.-28C>A	5_prime_UTR_variant	1/12	1		A1	Q96GX5-3
MASTL	ENST00000342386.10 linkuse as main transcript	c.-28C>A	5_prime_UTR_variant	1/11	2			Q96GX5-2

Frequencies

GnomAD3 genomes

AF:

0.602

AC:

91400

AN:

151786

Hom.:

27804

Cov.:

show subpopulations

Gnomad AFR

AF:

0.557

Gnomad AMI

AF:

0.622

Gnomad AMR

AF:

0.570

Gnomad ASJ

AF:

0.629

Gnomad EAS

AF:

0.427

Gnomad SAS

AF:

0.477

Gnomad FIN

AF:

0.662

Gnomad MID

AF:

0.583

Gnomad NFE

AF:

0.648

Gnomad OTH

AF:

0.592

GnomAD3 exomes

AF:

0.592

AC:

115272

AN:

194594

Hom.:

34644

AF XY:

0.590

AC XY:

62832

AN XY:

106548

show subpopulations

Gnomad AFR exome

AF:

0.554

Gnomad AMR exome

AF:

0.541

Gnomad ASJ exome

AF:

0.616

Gnomad EAS exome

AF:

0.441

Gnomad SAS exome

AF:

0.488

Gnomad FIN exome

AF:

0.670

Gnomad NFE exome

AF:

0.653

Gnomad OTH exome

AF:

0.625

GnomAD4 exome

AF:

0.626

AC:

891481

AN:

1423946

Hom.:

282083

Cov.:

AF XY:

0.623

AC XY:

439517

AN XY:

705682

show subpopulations

Gnomad4 AFR exome

AF:

0.559

Gnomad4 AMR exome

AF:

0.541

Gnomad4 ASJ exome

AF:

0.620

Gnomad4 EAS exome

AF:

0.399

Gnomad4 SAS exome

AF:

0.492

Gnomad4 FIN exome

AF:

0.663

Gnomad4 NFE exome

AF:

0.648

Gnomad4 OTH exome

AF:

0.612

GnomAD4 genome

AF:

0.602

AC:

91406

AN:

151900

Hom.:

27801

Cov.:

AF XY:

0.601

AC XY:

44600

AN XY:

74238

show subpopulations

Gnomad4 AFR

AF:

0.556

Gnomad4 AMR

AF:

0.570

Gnomad4 ASJ

AF:

0.629

Gnomad4 EAS

AF:

0.426

Gnomad4 SAS

AF:

0.479

Gnomad4 FIN

AF:

0.662

Gnomad4 NFE

AF:

0.648

Gnomad4 OTH

AF:

0.585

Alfa

AF:

0.628

Hom.:

5507

Bravo

AF:

0.594

Asia WGS

AF:

0.445

AC:

1549

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Thrombocytopenia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

Cadd

Benign

8.0

Dann

Benign

0.72

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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