rs36121140

Positions:

chr10-27169969-C-A

Variant summary

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

The NM_001172303.3(MASTL):c.1010C>A(p.Thr337Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00557 in 1,614,016 control chromosomes in the GnomAD database, including 302 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0057 ( 38 hom., cov: 33)

Exomes 𝑓: 0.0056 ( 264 hom. )

Consequence

MASTL
NM_001172303.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.108

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:

ACBD5 (HGNC:23338): (acyl-CoA binding domain containing 5) This gene encodes a member of the acyl-Coenzyme A binding protein family, known to function in the transport and distribution of long chain acyl-Coenzyme A in cells. This gene may play a role in the differentiation of megakaryocytes and formation of platelets. A related protein in yeast is involved in autophagy of peroxisomes. A mutation in this gene has been associated with autosomal dominant thrombocytopenia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

ACBD5 links:

MASTL (HGNC:):

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 (MetaRNN=0.0025212765).

BP6

Variant 10-27169969-C-A is Benign according to our data. Variant chr10-27169969-C-A is described in ClinVar as [Benign]. Clinvar id is 262114.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MASTL	NM_001172303.3 linkuse as main transcript	c.1010C>A	p.Thr337Lys	missense_variant	8/12	ENST00000375940.9	NP_001165774.1	Q96GX5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MASTL	ENST00000375940.9 linkuse as main transcript	c.1010C>A	p.Thr337Lys	missense_variant	8/12	1	NM_001172303.3	ENSP00000365107.5		Q96GX5-1

Frequencies

GnomAD3 genomes

AF:

0.00574

AC:

873

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000628

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.110

Gnomad SAS

AF:

0.0226

Gnomad FIN

AF:

0.00132

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00154

Gnomad OTH

AF:

0.00957

GnomAD3 exomes

AF:

0.0117

AC:

2940

AN:

250774

Hom.:

122

AF XY:

0.0119

AC XY:

1607

AN XY:

135552

show subpopulations

Gnomad AFR exome

AF:

0.000925

Gnomad AMR exome

AF:

0.00110

Gnomad ASJ exome

AF:

0.000497

Gnomad EAS exome

AF:

0.112

Gnomad SAS exome

AF:

0.0178

Gnomad FIN exome

AF:

0.00166

Gnomad NFE exome

AF:

0.00177

Gnomad OTH exome

AF:

0.00638

GnomAD4 exome

AF:

0.00555

AC:

8115

AN:

1461820

Hom.:

264

Cov.:

AF XY:

0.00598

AC XY:

4351

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.00119

Gnomad4 AMR exome

AF:

0.00114

Gnomad4 ASJ exome

AF:

0.000765

Gnomad4 EAS exome

AF:

0.100

Gnomad4 SAS exome

AF:

0.0186

Gnomad4 FIN exome

AF:

0.00225

Gnomad4 NFE exome

AF:

0.00154

Gnomad4 OTH exome

AF:

0.00934

GnomAD4 genome

AF:

0.00574

AC:

873

AN:

152196

Hom.:

Cov.:

AF XY:

0.00660

AC XY:

491

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.000626

Gnomad4 AMR

AF:

0.00177

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.110

Gnomad4 SAS

AF:

0.0224

Gnomad4 FIN

AF:

0.00132

Gnomad4 NFE

AF:

0.00154

Gnomad4 OTH

AF:

0.00994

Alfa

AF:

0.00567

Hom.:

Bravo

AF:

0.00624

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00285

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00198

AC:

ExAC

AF:

0.0117

AC:

1416

Asia WGS

AF:

0.0420

AC:

146

AN:

3476

EpiCase

AF:

0.00169

EpiControl

AF:

0.00119

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

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

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

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.55

CADD

Benign

3.3

DANN

Benign

0.37

DEOGEN2

Benign

0.014

.;T;.;.

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.60

T;T;T;T

MetaRNN

Benign

0.0025

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

L;L;L;.

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.1

N;N;N;.

REVEL

Benign

0.033

Sift

Benign

0.060

T;T;T;.

Sift4G

Benign

0.88

T;T;T;T

Polyphen

0.0030

B;B;B;.

Vest4

0.034

MPC

0.13

ClinPred

0.0020

GERP RS

0.79

Varity_R

0.034

gMVP

0.33

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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