rs56204835

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_001172303.3(MASTL):c.477G>A(p.Pro159Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00107 in 1,611,822 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0054 ( 10 hom., cov: 31)

Exomes 𝑓: 0.00062 ( 8 hom. )

Consequence

MASTL
NM_001172303.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.11

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

autosomal thrombocytopenia with normal platelets
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

MASTL links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant 10-27161106-G-A is Benign according to our data. Variant chr10-27161106-G-A is described in ClinVar as Benign. ClinVar VariationId is 262125.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.11 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00542 (824/152096) while in subpopulation AFR AF = 0.0188 (778/41458). AF 95% confidence interval is 0.0177. There are 10 homozygotes in GnomAd4. There are 397 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High AC in GnomAd4 at 824 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MASTL	NM_001172303.3 link	c.477G>A	p.Pro159Pro	synonymous_variant	Exon 4 of 12	ENST00000375940.9	NP_001165774.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
MASTL	ENST00000375940.9 link	c.477G>A	p.Pro159Pro	synonymous_variant	Exon 4 of 12	1	NM_001172303.3	ENSP00000365107.5
MASTL	ENST00000375946.8 link	c.477G>A	p.Pro159Pro	synonymous_variant	Exon 4 of 12	1		ENSP00000365113.4
MASTL	ENST00000342386.10 link	c.477G>A	p.Pro159Pro	synonymous_variant	Exon 4 of 11	2		ENSP00000343446.5

Frequencies

GnomAD3 genomes

AF:

0.00541

AC:

822

AN:

151976

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0188

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00197

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00382

GnomAD2 exomes

AF:

0.00150

AC:

376

AN:

251464

AF XY:

0.00110

show subpopulations

Gnomad AFR exome

AF:

0.0193

Gnomad AMR exome

AF:

0.000607

Gnomad ASJ exome

AF:

0.00238

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000105

Gnomad OTH exome

AF:

0.000815

GnomAD4 exome

AF:

0.000615

AC:

898

AN:

1459726

Hom.:

Cov.:

AF XY:

0.000505

AC XY:

367

AN XY:

726360

show subpopulations

African (AFR)

AF:

0.0194

AC:

649

AN:

33414

American (AMR)

AF:

0.000716

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00226

AC:

AN:

26110

East Asian (EAS)

AF:

0.00

AC:

AN:

39668

South Asian (SAS)

AF:

0.0000812

AC:

AN:

86200

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53406

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.0000631

AC:

AN:

1110126

Other (OTH)

AF:

0.00131

AC:

AN:

60320

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.449

Heterozygous variant carriers

146

195

244

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00542

AC:

824

AN:

152096

Hom.:

Cov.:

AF XY:

0.00534

AC XY:

397

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.0188

AC:

778

AN:

41458

American (AMR)

AF:

0.00196

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.000208

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10582

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68000

Other (OTH)

AF:

0.00378

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

130

174

217

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00273

Hom.:

Bravo

AF:

0.00623

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jan 11, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Thrombocytopenia

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

-0.37

CADD

Benign

(source)

DANN

Benign

0.66

PhyloP100

2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over