10-27155777-A-T

Position:

• chr10-27155777-A-T

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.186+165A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0751 in 152,156 control chromosomes in the GnomAD database, including 496 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.075 (496 hom., cov: 32)
• Consequence: MASTL NM_001172303.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.21

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=-0.91).
• BP6: Variant 10-27155777-A-T is Benign according to our data. Variant chr10-27155777-A-T is described in ClinVar as [Benign]. Clinvar id is 1268165.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MASTL	NM_001172303.3	c.186+165A>T		intron_variant		ENST00000375940.9	NP_001165774.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MASTL	ENST00000375940.9	c.186+165A>T		intron_variant		1	NM_001172303.3	ENSP00000365107	P5
MASTL	ENST00000375946.8	c.186+165A>T		intron_variant		1		ENSP00000365113	A1
MASTL	ENST00000342386.10	c.186+165A>T		intron_variant		2		ENSP00000343446

Frequencies

GnomAD3 genomes AF: 0.0750 AC: 11408 AN: 152038 Hom.: 495 Cov.: 32

Gnomad AFR AF: 0.0921

Gnomad AMI AF: 0.0220

Gnomad AMR AF: 0.0514

Gnomad ASJ AF: 0.0773

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0541

Gnomad OTH AF: 0.0540

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

GnomAD4 genome AF: 0.0751 AC: 11429 AN: 152156 Hom.: 496 Cov.: 32 AF XY: 0.0791 AC XY: 5887 AN XY: 74384

Gnomad4 AFR AF: 0.0926

Gnomad4 AMR AF: 0.0513

Gnomad4 ASJ AF: 0.0773

Gnomad4 EAS AF: 0.160

Gnomad4 SAS AF: 0.155

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.0541

Gnomad4 OTH AF: 0.0539

Alfa AF: 0.0717 Hom.: 56

Bravo AF: 0.0713

Asia WGS AF: 0.154 AC: 536 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 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.31
DANN	Benign	0.53

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: rs3824592; hg19: chr10-27444706; COSMIC: COSV58761834; COSMIC: COSV58761834;