10-27161062-G-C

Variant names:

• chr10-27161062-G-C
• rs12572707
• NM_001172303.3:c.465-32G>C

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.465-32G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0682 in 1,368,716 control chromosomes in the GnomAD database, including 4,308 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.075 (497 hom., cov: 31)
  • Exomes 𝑓: 0.067 (3811 hom.)
• Consequence: MASTL NM_001172303.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0140
• Publications: 6 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=-0.83).
• BP6: Variant 10-27161062-G-C is Benign according to our data. Variant chr10-27161062-G-C is described in ClinVar as Benign. ClinVar VariationId is 262124.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MASTL	NM_001172303.3	c.465-32G>C		intron_variant	Intron 3 of 11	ENST00000375940.9	NP_001165774.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MASTL	ENST00000375940.9	c.465-32G>C		intron_variant	Intron 3 of 11	1	NM_001172303.3	ENSP00000365107.5
MASTL	ENST00000375946.8	c.465-32G>C		intron_variant	Intron 3 of 11	1		ENSP00000365113.4
MASTL	ENST00000342386.10	c.465-32G>C		intron_variant	Intron 3 of 10	2		ENSP00000343446.5

Frequencies

GnomAD3 genomes AF: 0.0753 AC: 11415 AN: 151562 Hom.: 495 Cov.: 31

Gnomad AFR AF: 0.0924

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0516

Gnomad ASJ AF: 0.0772

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0543

Gnomad OTH AF: 0.0542

GnomAD2 exomes AF: 0.0835 AC: 20742 AN: 248298 AF XY: 0.0853

Gnomad AFR exome AF: 0.0926

Gnomad AMR exome AF: 0.0673

Gnomad ASJ exome AF: 0.0733

Gnomad EAS exome AF: 0.151

Gnomad FIN exome AF: 0.113

Gnomad NFE exome AF: 0.0553

Gnomad OTH exome AF: 0.0687

GnomAD4 exome AF: 0.0674 AC: 81972 AN: 1217036 Hom.: 3811 Cov.: 17 AF XY: 0.0697 AC XY: 43081 AN XY: 617688

African (AFR) AF: 0.0952 AC: 2697 AN: 28316

American (AMR) AF: 0.0647 AC: 2786 AN: 43064

Ashkenazi Jewish (ASJ) AF: 0.0742 AC: 1815 AN: 24462

East Asian (EAS) AF: 0.207 AC: 7988 AN: 38498

South Asian (SAS) AF: 0.144 AC: 11658 AN: 80678

European-Finnish (FIN) AF: 0.109 AC: 5788 AN: 53238

Middle Eastern (MID) AF: 0.0488 AC: 258 AN: 5288

European-Non Finnish (NFE) AF: 0.0510 AC: 45441 AN: 891412

Other (OTH) AF: 0.0680 AC: 3541 AN: 52080

GnomAD4 genome AF: 0.0754 AC: 11437 AN: 151680 Hom.: 497 Cov.: 31 AF XY: 0.0795 AC XY: 5893 AN XY: 74114

African (AFR) AF: 0.0929 AC: 3846 AN: 41390

American (AMR) AF: 0.0515 AC: 784 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.0772 AC: 268 AN: 3470

East Asian (EAS) AF: 0.160 AC: 826 AN: 5174

South Asian (SAS) AF: 0.156 AC: 751 AN: 4816

European-Finnish (FIN) AF: 0.109 AC: 1133 AN: 10414

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

European-Non Finnish (NFE) AF: 0.0543 AC: 3684 AN: 67874

Other (OTH) AF: 0.0541 AC: 114 AN: 2106

Alfa AF: 0.0423 Hom.: 51

Bravo AF: 0.0713

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

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	-0.83
CADD	Benign	1.4
DANN	Benign	0.58
PhyloP100		-0.014
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs12572707; hg19: chr10-27449991; COSMIC: COSV60910579;