10-27155400-T-C

Variant summary

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

The NM_001172303.3(MASTL):c.-27T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.785 in 1,577,752 control chromosomes in the GnomAD database, including 487,571 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.79 ( 47979 hom., cov: 32)

Exomes 𝑓: 0.78 ( 439592 hom. )

Consequence

MASTL
NM_001172303.3 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -4.35

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=-0.81).

BP6

Variant 10-27155400-T-C is Benign according to our data. Variant chr10-27155400-T-C is described in ClinVar as [Benign]. Clinvar id is 262112.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.964 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.-27T>C		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.-27T>C	5_prime_UTR_variant	1/12	1	NM_001172303.3	P5	Q96GX5-1
MASTL	ENST00000375946.8 linkuse as main transcript	c.-27T>C	5_prime_UTR_variant	1/12	1		A1	Q96GX5-3
MASTL	ENST00000342386.10 linkuse as main transcript	c.-27T>C	5_prime_UTR_variant	1/11	2			Q96GX5-2

Frequencies

GnomAD3 genomes

AF:

0.793

AC:

120390

AN:

151830

Hom.:

47953

Cov.:

show subpopulations

Gnomad AFR

AF:

0.798

Gnomad AMI

AF:

0.778

Gnomad AMR

AF:

0.741

Gnomad ASJ

AF:

0.778

Gnomad EAS

AF:

0.987

Gnomad SAS

AF:

0.833

Gnomad FIN

AF:

0.879

Gnomad MID

AF:

0.736

Gnomad NFE

AF:

0.772

Gnomad OTH

AF:

0.779

GnomAD3 exomes

AF:

0.799

AC:

157070

AN:

196508

Hom.:

63107

AF XY:

0.800

AC XY:

86105

AN XY:

107612

show subpopulations

Gnomad AFR exome

AF:

0.790

Gnomad AMR exome

AF:

0.720

Gnomad ASJ exome

AF:

0.779

Gnomad EAS exome

AF:

0.988

Gnomad SAS exome

AF:

0.823

Gnomad FIN exome

AF:

0.879

Gnomad NFE exome

AF:

0.775

Gnomad OTH exome

AF:

0.793

GnomAD4 exome

AF:

0.784

AC:

1117627

AN:

1425804

Hom.:

439592

Cov.:

AF XY:

0.785

AC XY:

554701

AN XY:

706760

show subpopulations

Gnomad4 AFR exome

AF:

0.793

Gnomad4 AMR exome

AF:

0.717

Gnomad4 ASJ exome

AF:

0.778

Gnomad4 EAS exome

AF:

0.983

Gnomad4 SAS exome

AF:

0.819

Gnomad4 FIN exome

AF:

0.871

Gnomad4 NFE exome

AF:

0.772

Gnomad4 OTH exome

AF:

0.789

GnomAD4 genome

AF:

0.793

AC:

120466

AN:

151948

Hom.:

47979

Cov.:

AF XY:

0.801

AC XY:

59519

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.797

Gnomad4 AMR

AF:

0.740

Gnomad4 ASJ

AF:

0.778

Gnomad4 EAS

AF:

0.987

Gnomad4 SAS

AF:

0.833

Gnomad4 FIN

AF:

0.879

Gnomad4 NFE

AF:

0.772

Gnomad4 OTH

AF:

0.781

Alfa

AF:

0.741

Hom.:

4629

Bravo

AF:

0.781

Asia WGS

AF:

0.884

AC:

3073

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

-0.81

Cadd

Benign

0.47

Dann

Benign

0.48

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