rs16927590

Variant names:

• chr10-27158836-G-A
• rs16927590
• NM_001172303.3:c.324+150G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-27158836-G-A
• chr10-27158836-G-C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001172303.3(MASTL):​c.324+150G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0303 in 792,330 control chromosomes in the GnomAD database, including 3,563 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.10 (2527 hom., cov: 32)
  • Exomes 𝑓: 0.014 (1036 hom.)
• Consequence: MASTL NM_001172303.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.328
• Publications: 0 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 10-27158836-G-A is Benign according to our data. Variant chr10-27158836-G-A is described in CliVar as Benign. Clinvar id is 1231784.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-27158836-G-A is described in CliVar as Benign. Clinvar id is 1231784.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-27158836-G-A is described in CliVar as Benign. Clinvar id is 1231784.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-27158836-G-A is described in CliVar as Benign. Clinvar id is 1231784.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-27158836-G-A is described in CliVar as Benign. Clinvar id is 1231784.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-27158836-G-A is described in CliVar as Benign. Clinvar id is 1231784.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-27158836-G-A is described in CliVar as Benign. Clinvar id is 1231784.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-27158836-G-A is described in CliVar as Benign. Clinvar id is 1231784.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-27158836-G-A is described in CliVar as Benign. Clinvar id is 1231784.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-27158836-G-A is described in CliVar as Benign. Clinvar id is 1231784.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-27158836-G-A is described in CliVar as Benign. Clinvar id is 1231784.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-27158836-G-A is described in CliVar as Benign. Clinvar id is 1231784.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-27158836-G-A is described in CliVar as Benign. Clinvar id is 1231784.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-27158836-G-A is described in CliVar as Benign. Clinvar id is 1231784.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-27158836-G-A is described in CliVar as Benign. Clinvar id is 1231784.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-27158836-G-A is described in CliVar as Benign. Clinvar id is 1231784.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-27158836-G-A is described in CliVar as Benign. Clinvar id is 1231784.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-27158836-G-A is described in CliVar as Benign. Clinvar id is 1231784.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-27158836-G-A is described in CliVar as Benign. Clinvar id is 1231784.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-27158836-G-A is described in CliVar as Benign. Clinvar id is 1231784.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-27158836-G-A is described in CliVar as Benign. Clinvar id is 1231784.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-27158836-G-A is described in CliVar as Benign. Clinvar id is 1231784.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-27158836-G-A is described in CliVar as Benign. Clinvar id is 1231784.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MASTL	NM_001172303.3	c.324+150G>A		intron_variant	Intron 2 of 11	ENST00000375940.9	NP_001165774.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MASTL	ENST00000375940.9	c.324+150G>A		intron_variant	Intron 2 of 11	1	NM_001172303.3	ENSP00000365107.5
MASTL	ENST00000375946.8	c.324+150G>A		intron_variant	Intron 2 of 11	1		ENSP00000365113.4
MASTL	ENST00000342386.10	c.324+150G>A		intron_variant	Intron 2 of 10	2		ENSP00000343446.5

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15311 AN: 152058 Hom.: 2526 Cov.: 32

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0374

Gnomad ASJ AF: 0.0363

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00225

Gnomad OTH AF: 0.0705

GnomAD4 exome AF: 0.0136 AC: 8690 AN: 640154 Hom.: 1036 AF XY: 0.0114 AC XY: 3906 AN XY: 342500

African (AFR) AF: 0.334 AC: 5538 AN: 16576

American (AMR) AF: 0.0197 AC: 653 AN: 33184

Ashkenazi Jewish (ASJ) AF: 0.0393 AC: 749 AN: 19062

East Asian (EAS) AF: 0.00 AC: 0 AN: 34224

South Asian (SAS) AF: 0.000781 AC: 49 AN: 62710

European-Finnish (FIN) AF: 0.0000537 AC: 2 AN: 37218

Middle Eastern (MID) AF: 0.0193 AC: 57 AN: 2956

European-Non Finnish (NFE) AF: 0.00161 AC: 646 AN: 401124

Other (OTH) AF: 0.0301 AC: 996 AN: 33100

GnomAD4 genome AF: 0.101 AC: 15328 AN: 152176 Hom.: 2527 Cov.: 32 AF XY: 0.0965 AC XY: 7178 AN XY: 74394

African (AFR) AF: 0.345 AC: 14322 AN: 41462

American (AMR) AF: 0.0373 AC: 571 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0363 AC: 126 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.00225 AC: 153 AN: 68026

Other (OTH) AF: 0.0697 AC: 147 AN: 2108

Alfa AF: 0.0838 Hom.: 292

Bravo AF: 0.115

Asia WGS AF: 0.0130 AC: 45 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 21, 2021

GeneDx

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	-0.88
CADD	Benign	5.1
DANN	Benign	0.81
PhyloP100		0.33
Mutation Taster		=99/1	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: rs16927590; hg19: chr10-27447765;