10-27158276-T-C

Position:

• chr10-27158276-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001172303.3(MASTL):​c.187-273T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 152,224 control chromosomes in the GnomAD database, including 1,903 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.14 (1903 hom., cov: 32)
• Consequence: MASTL NM_001172303.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.04

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 10-27158276-T-C is Benign according to our data. Variant chr10-27158276-T-C is described in ClinVar as [Benign]. Clinvar id is 1263152.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MASTL	NM_001172303.3	c.187-273T>C		intron_variant		ENST00000375940.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MASTL	ENST00000375940.9	c.187-273T>C		intron_variant		1	NM_001172303.3	P5
MASTL	ENST00000375946.8	c.187-273T>C		intron_variant		1		A1
MASTL	ENST00000342386.10	c.187-273T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21907 AN: 152106 Hom.: 1895 Cov.: 32

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.199

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.0104

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.0678

Gnomad MID AF: 0.213

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.173

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.144 AC: 21936 AN: 152224 Hom.: 1903 Cov.: 32 AF XY: 0.136 AC XY: 10129 AN XY: 74434

Gnomad4 AFR AF: 0.100

Gnomad4 AMR AF: 0.225

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.0104

Gnomad4 SAS AF: 0.112

Gnomad4 FIN AF: 0.0678

Gnomad4 NFE AF: 0.175

Gnomad4 OTH AF: 0.171

Alfa AF: 0.156 Hom.: 266

Bravo AF: 0.156

Asia WGS AF: 0.0680 AC: 238 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	13
DANN	Benign	0.76

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: rs788220; hg19: chr10-27447205;