rs41282218

Variant names:

• chr10-27155649-C-T
• rs41282218
• NM_001172303.3:c.186+37C>T

Variant summary

Our verdict is Benign. The variant received -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:3
• Conservation: PhyloP100: -0.532
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• autosomal thrombocytopenia with normal platelets

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
MASTL	NM_001172303.3	c.186+37C>T		intron_variant	Intron 1 of 11	ENST00000375940.9	NP_001165774.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MASTL	ENST00000375940.9	c.186+37C>T		intron_variant	Intron 1 of 11	1	NM_001172303.3	ENSP00000365107.5
MASTL	ENST00000375946.8	c.186+37C>T		intron_variant	Intron 1 of 11	1		ENSP00000365113.4
MASTL	ENST00000342386.10	c.186+37C>T		intron_variant	Intron 1 of 10	2		ENSP00000343446.5

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

GnomAD2 exomes AF: 0.0438 AC: 10819 AN: 246740 AF XY: 0.0435

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 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

African (AFR) AF: 0.0851 AC: 2840 AN: 33388

American (AMR) AF: 0.0198 AC: 885 AN: 44612

Ashkenazi Jewish (ASJ) AF: 0.0636 AC: 1661 AN: 26118

East Asian (EAS) AF: 0.00199 AC: 79 AN: 39666

South Asian (SAS) AF: 0.0349 AC: 3007 AN: 86122

European-Finnish (FIN) AF: 0.0557 AC: 2962 AN: 53188

Middle Eastern (MID) AF: 0.0408 AC: 230 AN: 5636

European-Non Finnish (NFE) AF: 0.0488 AC: 54116 AN: 1109100

Other (OTH) AF: 0.0480 AC: 2890 AN: 60230

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

African (AFR) AF: 0.0825 AC: 3429 AN: 41558

American (AMR) AF: 0.0331 AC: 506 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0674 AC: 234 AN: 3470

East Asian (EAS) AF: 0.00310 AC: 16 AN: 5168

South Asian (SAS) AF: 0.0325 AC: 157 AN: 4830

European-Finnish (FIN) AF: 0.0520 AC: 552 AN: 10616

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0514 AC: 3496 AN: 68018

Other (OTH) AF: 0.0440 AC: 93 AN: 2116

Alfa AF: 0.0581 Hom.: 56

Bravo AF: 0.0561

Asia WGS AF: 0.0350 AC: 123 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.9
DANN	Benign	0.83
PhyloP100		-0.53
PromoterAI		-0.23	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs41282218; hg19: chr10-27444578;