10-27155321-T-C

Position:

• chr10-27155321-T-C

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The ENST00000375946.8(MASTL):​c.-106T>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 0.00593 in 1,207,364 control chromosomes in the GnomAD database, including 263 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0057 (36 hom., cov: 32)
  • Exomes 𝑓: 0.0060 (227 hom.)
• Consequence: MASTL ENST00000375946.8 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.37

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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 10-27155321-T-C is Benign according to our data. Variant chr10-27155321-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 299784.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MASTL	NM_001172303.3			upstream_gene_variant		ENST00000375940.9	NP_001165774.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MASTL	ENST00000375946.8	c.-106T>C		5_prime_UTR_variant	1/12	1		ENSP00000365113	A1
MASTL	ENST00000375940.9			upstream_gene_variant		1	NM_001172303.3	ENSP00000365107	P5
MASTL	ENST00000342386.10			upstream_gene_variant		2		ENSP00000343446

Frequencies

GnomAD3 genomes AF: 0.00566 AC: 860 AN: 152022 Hom.: 36 Cov.: 32

Gnomad AFR AF: 0.000531

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00177

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.0226

Gnomad FIN AF: 0.00132

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00154

Gnomad OTH AF: 0.00959

GnomAD4 exome AF: 0.00597 AC: 6302 AN: 1055224 Hom.: 227 Cov.: 14 AF XY: 0.00650 AC XY: 3402 AN XY: 523420

Gnomad4 AFR exome AF: 0.000820

Gnomad4 AMR exome AF: 0.00105

Gnomad4 ASJ exome AF: 0.000848

Gnomad4 EAS exome AF: 0.0994

Gnomad4 SAS exome AF: 0.0181

Gnomad4 FIN exome AF: 0.00268

Gnomad4 NFE exome AF: 0.00152

Gnomad4 OTH exome AF: 0.00944

GnomAD4 genome AF: 0.00565 AC: 860 AN: 152140 Hom.: 36 Cov.: 32 AF XY: 0.00643 AC XY: 478 AN XY: 74350

Gnomad4 AFR AF: 0.000530

Gnomad4 AMR AF: 0.00176

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.110

Gnomad4 SAS AF: 0.0224

Gnomad4 FIN AF: 0.00132

Gnomad4 NFE AF: 0.00154

Gnomad4 OTH AF: 0.00996

Alfa AF: 0.000721 Hom.: 0

Bravo AF: 0.00620

Asia WGS AF: 0.0420 AC: 145 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Thrombocytopenia Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	18
DANN	Benign	0.89

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: rs3824594; hg19: chr10-27444250;