NM_001172303.3:c.812-28G>A

Variant names:

• chr10-27167074-G-A
• rs788238
• NM_001172303.3:c.812-28G>A

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.812-28G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.999 in 1,593,372 control chromosomes in the GnomAD database, including 794,749 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.99 (75192 hom., cov: 31)
  • Exomes 𝑓: 1.0 (719557 hom.)
• Consequence: MASTL NM_001172303.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.101
• Publications: 7 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=-0.88).
• BP6: Variant 10-27167074-G-A is Benign according to our data. Variant chr10-27167074-G-A is described in CliVar as Benign. Clinvar id is 262127.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-27167074-G-A is described in CliVar as Benign. Clinvar id is 262127.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-27167074-G-A is described in CliVar as Benign. Clinvar id is 262127.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-27167074-G-A is described in CliVar as Benign. Clinvar id is 262127.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-27167074-G-A is described in CliVar as Benign. Clinvar id is 262127.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-27167074-G-A is described in CliVar as Benign. Clinvar id is 262127.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-27167074-G-A is described in CliVar as Benign. Clinvar id is 262127.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-27167074-G-A is described in CliVar as Benign. Clinvar id is 262127.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-27167074-G-A is described in CliVar as Benign. Clinvar id is 262127.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-27167074-G-A is described in CliVar as Benign. Clinvar id is 262127.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-27167074-G-A is described in CliVar as Benign. Clinvar id is 262127.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-27167074-G-A is described in CliVar as Benign. Clinvar id is 262127.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-27167074-G-A is described in CliVar as Benign. Clinvar id is 262127.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-27167074-G-A is described in CliVar as Benign. Clinvar id is 262127.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-27167074-G-A is described in CliVar as Benign. Clinvar id is 262127.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-27167074-G-A is described in CliVar as Benign. Clinvar id is 262127.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-27167074-G-A is described in CliVar as Benign. Clinvar id is 262127.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-27167074-G-A is described in CliVar as Benign. Clinvar id is 262127.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-27167074-G-A is described in CliVar as Benign. Clinvar id is 262127.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-27167074-G-A is described in CliVar as Benign. Clinvar id is 262127.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-27167074-G-A is described in CliVar as Benign. Clinvar id is 262127.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-27167074-G-A is described in CliVar as Benign. Clinvar id is 262127.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-27167074-G-A is described in CliVar as Benign. Clinvar id is 262127.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MASTL	NM_001172303.3	c.812-28G>A		intron_variant	Intron 6 of 11	ENST00000375940.9	NP_001165774.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MASTL	ENST00000375940.9	c.812-28G>A		intron_variant	Intron 6 of 11	1	NM_001172303.3	ENSP00000365107.5
MASTL	ENST00000375946.8	c.812-28G>A		intron_variant	Intron 6 of 11	1		ENSP00000365113.4
MASTL	ENST00000342386.10	c.812-28G>A		intron_variant	Intron 6 of 10	2		ENSP00000343446.5

Frequencies

GnomAD3 genomes AF: 0.994 AC: 151220 AN: 152182 Hom.: 75138 Cov.: 31

Gnomad AFR AF: 0.978

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.997

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.995

GnomAD2 exomes AF: 0.998 AC: 250720 AN: 251112 AF XY: 0.999

Gnomad AFR exome AF: 0.979

Gnomad AMR exome AF: 0.999

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 1.00

GnomAD4 exome AF: 0.999 AC: 1440077 AN: 1441072 Hom.: 719557 Cov.: 26 AF XY: 0.999 AC XY: 717962 AN XY: 718386

African (AFR) AF: 0.976 AC: 32194 AN: 32994

American (AMR) AF: 0.999 AC: 44645 AN: 44704

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 26012 AN: 26012

East Asian (EAS) AF: 1.00 AC: 39552 AN: 39552

South Asian (SAS) AF: 1.00 AC: 85806 AN: 85808

European-Finnish (FIN) AF: 1.00 AC: 53250 AN: 53250

Middle Eastern (MID) AF: 0.999 AC: 5727 AN: 5732

European-Non Finnish (NFE) AF: 1.00 AC: 1093274 AN: 1093306

Other (OTH) AF: 0.998 AC: 59617 AN: 59714

GnomAD4 genome AF: 0.994 AC: 151333 AN: 152300 Hom.: 75192 Cov.: 31 AF XY: 0.994 AC XY: 74009 AN XY: 74462

African (AFR) AF: 0.978 AC: 40642 AN: 41552

American (AMR) AF: 0.997 AC: 15246 AN: 15290

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5176 AN: 5176

South Asian (SAS) AF: 1.00 AC: 4821 AN: 4822

European-Finnish (FIN) AF: 1.00 AC: 10623 AN: 10624

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68047 AN: 68048

Other (OTH) AF: 0.995 AC: 2100 AN: 2110

Alfa AF: 0.997 Hom.: 14425

Bravo AF: 0.993

Asia WGS AF: 0.996 AC: 3464 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

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

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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	-0.88
CADD	Benign	6.2
DANN	Benign	0.39
PhyloP100		0.10
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)		0.020		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: rs788238; hg19: chr10-27456003;