10-27155415-T-G

Position:

• chr10-27155415-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.987

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]

ACMG classification

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	Protein	UniProt
MASTL	NM_001172303.3	c.-12T>G		5_prime_UTR_variant	1/12	ENST00000375940.9	NP_001165774.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.845 AC: 128472 AN: 152020 Hom.: 54559 Cov.: 32

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

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.: 44 AF XY: 0.831 AC XY: 597913 AN XY: 719118

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.: 32 AF XY: 0.853 AC XY: 63407 AN XY: 74370

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:4

Revision: criteria provided, multiple submitters, no conflicts

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	-	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

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

Other links and lift over

dbSNP: rs7907988; hg19: chr10-27444344;