10-27155400-T-C

Position:

• chr10-27155400-T-C

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.-27T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.785 in 1,577,752 control chromosomes in the GnomAD database, including 487,571 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.79 (47979 hom., cov: 32)
  • Exomes 𝑓: 0.78 (439592 hom.)
• Consequence: MASTL NM_001172303.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -4.35

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 10-27155400-T-C is Benign according to our data. Variant chr10-27155400-T-C is described in ClinVar as [Benign]. Clinvar id is 262112.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.964 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MASTL	NM_001172303.3	c.-27T>C		5_prime_UTR_variant	1/12	ENST00000375940.9	NP_001165774.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MASTL	ENST00000375940.9	c.-27T>C		5_prime_UTR_variant	1/12	1	NM_001172303.3	ENSP00000365107	P5
MASTL	ENST00000375946.8	c.-27T>C		5_prime_UTR_variant	1/12	1		ENSP00000365113	A1
MASTL	ENST00000342386.10	c.-27T>C		5_prime_UTR_variant	1/11	2		ENSP00000343446

Frequencies

GnomAD3 genomes AF: 0.793 AC: 120390 AN: 151830 Hom.: 47953 Cov.: 32

Gnomad AFR AF: 0.798

Gnomad AMI AF: 0.778

Gnomad AMR AF: 0.741

Gnomad ASJ AF: 0.778

Gnomad EAS AF: 0.987

Gnomad SAS AF: 0.833

Gnomad FIN AF: 0.879

Gnomad MID AF: 0.736

Gnomad NFE AF: 0.772

Gnomad OTH AF: 0.779

GnomAD3 exomes AF: 0.799 AC: 157070 AN: 196508 Hom.: 63107 AF XY: 0.800 AC XY: 86105 AN XY: 107612

Gnomad AFR exome AF: 0.790

Gnomad AMR exome AF: 0.720

Gnomad ASJ exome AF: 0.779

Gnomad EAS exome AF: 0.988

Gnomad SAS exome AF: 0.823

Gnomad FIN exome AF: 0.879

Gnomad NFE exome AF: 0.775

Gnomad OTH exome AF: 0.793

GnomAD4 exome AF: 0.784 AC: 1117627 AN: 1425804 Hom.: 439592 Cov.: 35 AF XY: 0.785 AC XY: 554701 AN XY: 706760

Gnomad4 AFR exome AF: 0.793

Gnomad4 AMR exome AF: 0.717

Gnomad4 ASJ exome AF: 0.778

Gnomad4 EAS exome AF: 0.983

Gnomad4 SAS exome AF: 0.819

Gnomad4 FIN exome AF: 0.871

Gnomad4 NFE exome AF: 0.772

Gnomad4 OTH exome AF: 0.789

GnomAD4 genome AF: 0.793 AC: 120466 AN: 151948 Hom.: 47979 Cov.: 32 AF XY: 0.801 AC XY: 59519 AN XY: 74276

Gnomad4 AFR AF: 0.797

Gnomad4 AMR AF: 0.740

Gnomad4 ASJ AF: 0.778

Gnomad4 EAS AF: 0.987

Gnomad4 SAS AF: 0.833

Gnomad4 FIN AF: 0.879

Gnomad4 NFE AF: 0.772

Gnomad4 OTH AF: 0.781

Alfa AF: 0.741 Hom.: 4629

Bravo AF: 0.781

Asia WGS AF: 0.884 AC: 3073 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Thrombocytopenia Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.47
DANN	Benign	0.48
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs7907981; hg19: chr10-27444329;