Variant chr10-27155374-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001172303.3(MASTL):c.-53G>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 0.603 in 1,531,026 control chromosomes in the GnomAD database, including 287,460 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.50 ( 21703 hom., cov: 32)

Exomes 𝑓: 0.61 ( 265757 hom. )

Consequence

MASTL
NM_001172303.3 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.172

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=-0.67).

BP6

Variant 10-27155374-G-A is Benign according to our data. Variant chr10-27155374-G-A is described in ClinVar as [Benign]. Clinvar id is 299785.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.641 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.-53G>A		5_prime_UTR_variant	1/12	ENST00000375940.9	NP_001165774.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MASTL	ENST00000375940.9 linkuse as main transcript	c.-53G>A	5_prime_UTR_variant	1/12	1	NM_001172303.3	ENSP00000365107	P5	Q96GX5-1
MASTL	ENST00000375946.8 linkuse as main transcript	c.-53G>A	5_prime_UTR_variant	1/12	1		ENSP00000365113	A1	Q96GX5-3
MASTL	ENST00000342386.10 linkuse as main transcript	c.-53G>A	5_prime_UTR_variant	1/11	2		ENSP00000343446		Q96GX5-2

Frequencies

GnomAD3 genomes

AF:

0.500

AC:

75985

AN:

151878

Hom.:

21712

Cov.:

show subpopulations

Gnomad AFR

AF:

0.208

Gnomad AMI

AF:

0.622

Gnomad AMR

AF:

0.533

Gnomad ASJ

AF:

0.593

Gnomad EAS

AF:

0.426

Gnomad SAS

AF:

0.477

Gnomad FIN

AF:

0.662

Gnomad MID

AF:

0.564

Gnomad NFE

AF:

0.646

Gnomad OTH

AF:

0.522

GnomAD4 exome

AF:

0.614

AC:

846597

AN:

1379028

Hom.:

265757

Cov.:

AF XY:

0.612

AC XY:

416450

AN XY:

680750

show subpopulations

Gnomad4 AFR exome

AF:

0.193

Gnomad4 AMR exome

AF:

0.518

Gnomad4 ASJ exome

AF:

0.580

Gnomad4 EAS exome

AF:

0.396

Gnomad4 SAS exome

AF:

0.491

Gnomad4 FIN exome

AF:

0.664

Gnomad4 NFE exome

AF:

0.646

Gnomad4 OTH exome

AF:

0.584

GnomAD4 genome

AF:

0.500

AC:

75973

AN:

151998

Hom.:

21703

Cov.:

AF XY:

0.503

AC XY:

37373

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.207

Gnomad4 AMR

AF:

0.532

Gnomad4 ASJ

AF:

0.593

Gnomad4 EAS

AF:

0.425

Gnomad4 SAS

AF:

0.478

Gnomad4 FIN

AF:

0.662

Gnomad4 NFE

AF:

0.646

Gnomad4 OTH

AF:

0.515

Alfa

AF:

0.445

Hom.:

1465

Bravo

AF:

0.478

Asia WGS

AF:

0.431

AC:

1500

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	- -
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 12, 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

-0.67

CADD

Benign

DANN

Benign

0.93

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