10-27155649-C-T

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.186+37C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0479 in 1,610,346 control chromosomes in the GnomAD database, including 2,032 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.056 (258 hom., cov: 33)
  • Exomes 𝑓: 0.047 (1774 hom.)
• Consequence: MASTL NM_001172303.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.532

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=-0.81).
• BP6: Variant 10-27155649-C-T is Benign according to our data. Variant chr10-27155649-C-T is described in ClinVar as [Benign]. Clinvar id is 262117.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0802 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MASTL	NM_001172303.3	c.186+37C>T		intron_variant		ENST00000375940.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MASTL	ENST00000375940.9	c.186+37C>T		intron_variant		1	NM_001172303.3	P5
MASTL	ENST00000375946.8	c.186+37C>T		intron_variant		1		A1
MASTL	ENST00000342386.10	c.186+37C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0558 AC: 8493 AN: 152170 Hom.: 256 Cov.: 33

Gnomad AFR AF: 0.0821

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0331

Gnomad ASJ AF: 0.0674

Gnomad EAS AF: 0.00309

Gnomad SAS AF: 0.0327

Gnomad FIN AF: 0.0520

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0514

Gnomad OTH AF: 0.0444

GnomAD3 exomes AF: 0.0438 AC: 10819 AN: 246740 Hom.: 302 AF XY: 0.0435 AC XY: 5821 AN XY: 133814

Gnomad AFR exome AF: 0.0833

Gnomad AMR exome AF: 0.0188

Gnomad ASJ exome AF: 0.0633

Gnomad EAS exome AF: 0.00344

Gnomad SAS exome AF: 0.0344

Gnomad FIN exome AF: 0.0556

Gnomad NFE exome AF: 0.0513

Gnomad OTH exome AF: 0.0418

GnomAD4 exome AF: 0.0471 AC: 68670 AN: 1458060 Hom.: 1774 Cov.: 32 AF XY: 0.0468 AC XY: 33959 AN XY: 725436

Gnomad4 AFR exome AF: 0.0851

Gnomad4 AMR exome AF: 0.0198

Gnomad4 ASJ exome AF: 0.0636

Gnomad4 EAS exome AF: 0.00199

Gnomad4 SAS exome AF: 0.0349

Gnomad4 FIN exome AF: 0.0557

Gnomad4 NFE exome AF: 0.0488

Gnomad4 OTH exome AF: 0.0480

GnomAD4 genome AF: 0.0559 AC: 8514 AN: 152286 Hom.: 258 Cov.: 33 AF XY: 0.0548 AC XY: 4079 AN XY: 74476

Gnomad4 AFR AF: 0.0825

Gnomad4 AMR AF: 0.0331

Gnomad4 ASJ AF: 0.0674

Gnomad4 EAS AF: 0.00310

Gnomad4 SAS AF: 0.0325

Gnomad4 FIN AF: 0.0520

Gnomad4 NFE AF: 0.0514

Gnomad4 OTH AF: 0.0440

Alfa AF: 0.0576 Hom.: 54

Bravo AF: 0.0561

Asia WGS AF: 0.0350 AC: 123 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	8.9
Dann	Benign	0.83

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

Other links and lift over

dbSNP: rs41282218; hg19: chr10-27444578;