10-27155415-T-G

Variant summary

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

The NM_001172303.3(MASTL):c.-12T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.832 in 1,599,164 control chromosomes in the GnomAD database, including 555,079 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.84 ( 54586 hom., cov: 32)

Exomes 𝑓: 0.83 ( 500493 hom. )

Consequence

MASTL
NM_001172303.3 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.987

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=-0.84).

BP6

Variant 10-27155415-T-G is Benign according to our data. Variant chr10-27155415-T-G is described in ClinVar as [Benign]. Clinvar id is 262111.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-27155415-T-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.967 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.-12T>G		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.-12T>G	5_prime_UTR_variant	1/12	1	NM_001172303.3	P5	Q96GX5-1
MASTL	ENST00000375946.8 linkuse as main transcript	c.-12T>G	5_prime_UTR_variant	1/12	1		A1	Q96GX5-3
MASTL	ENST00000342386.10 linkuse as main transcript	c.-12T>G	5_prime_UTR_variant	1/11	2			Q96GX5-2

Frequencies

GnomAD3 genomes

AF:

0.845

AC:

128472

AN:

152020

Hom.:

54559

Cov.:

show subpopulations

Gnomad AFR

AF:

0.867

Gnomad AMI

AF:

0.798

Gnomad AMR

AF:

0.773

Gnomad ASJ

AF:

0.845

Gnomad EAS

AF:

0.989

Gnomad SAS

AF:

0.865

Gnomad FIN

AF:

0.932

Gnomad MID

AF:

0.778

Gnomad NFE

AF:

0.824

Gnomad OTH

AF:

0.821

GnomAD3 exomes

AF:

0.842

AC:

189205

AN:

224638

Hom.:

80135

AF XY:

0.844

AC XY:

103318

AN XY:

122408

show subpopulations

Gnomad AFR exome

AF:

0.862

Gnomad AMR exome

AF:

0.735

Gnomad ASJ exome

AF:

0.842

Gnomad EAS exome

AF:

0.992

Gnomad SAS exome

AF:

0.858

Gnomad FIN exome

AF:

0.933

Gnomad NFE exome

AF:

0.827

Gnomad OTH exome

AF:

0.830

GnomAD4 exome

AF:

0.831

AC:

1202003

AN:

1447026

Hom.:

500493

Cov.:

AF XY:

0.831

AC XY:

597913

AN XY:

719118

show subpopulations

Gnomad4 AFR exome

AF:

0.864

Gnomad4 AMR exome

AF:

0.734

Gnomad4 ASJ exome

AF:

0.842

Gnomad4 EAS exome

AF:

0.985

Gnomad4 SAS exome

AF:

0.855

Gnomad4 FIN exome

AF:

0.926

Gnomad4 NFE exome

AF:

0.821

Gnomad4 OTH exome

AF:

0.836

GnomAD4 genome

AF:

0.845

AC:

128549

AN:

152138

Hom.:

54586

Cov.:

AF XY:

0.853

AC XY:

63407

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.866

Gnomad4 AMR

AF:

0.772

Gnomad4 ASJ

AF:

0.845

Gnomad4 EAS

AF:

0.989

Gnomad4 SAS

AF:

0.865

Gnomad4 FIN

AF:

0.932

Gnomad4 NFE

AF:

0.824

Gnomad4 OTH

AF:

0.823

Alfa

AF:

0.821

Hom.:

50766

Bravo

AF:

0.833

Asia WGS

AF:

0.915

AC:

3182

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

-0.84

Cadd

Benign

3.9

Dann

Benign

0.42

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