chr10-27155834-C-A

Position:

• chr10-27155834-C-A

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+222C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 151,870 control chromosomes in the GnomAD database, including 27,660 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.60 (27660 hom., cov: 30)
• Consequence: MASTL NM_001172303.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.78

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=-0.73).
• BP6: Variant 10-27155834-C-A is Benign according to our data. Variant chr10-27155834-C-A is described in ClinVar as [Benign]. Clinvar id is 1275356.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.644 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MASTL	NM_001172303.3	c.186+222C>A		intron_variant		ENST00000375940.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MASTL	ENST00000375940.9	c.186+222C>A		intron_variant		1	NM_001172303.3	P5
MASTL	ENST00000375946.8	c.186+222C>A		intron_variant		1		A1
MASTL	ENST00000342386.10	c.186+222C>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.601 AC: 91128 AN: 151752 Hom.: 27665 Cov.: 30

Gnomad AFR AF: 0.550

Gnomad AMI AF: 0.622

Gnomad AMR AF: 0.570

Gnomad ASJ AF: 0.629

Gnomad EAS AF: 0.425

Gnomad SAS AF: 0.477

Gnomad FIN AF: 0.663

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.649

Gnomad OTH AF: 0.593

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

GnomAD4 genome AF: 0.600 AC: 91133 AN: 151870 Hom.: 27660 Cov.: 30 AF XY: 0.599 AC XY: 44446 AN XY: 74178

Gnomad4 AFR AF: 0.549

Gnomad4 AMR AF: 0.569

Gnomad4 ASJ AF: 0.629

Gnomad4 EAS AF: 0.424

Gnomad4 SAS AF: 0.479

Gnomad4 FIN AF: 0.663

Gnomad4 NFE AF: 0.649

Gnomad4 OTH AF: 0.586

Alfa AF: 0.542 Hom.: 2114

Bravo AF: 0.592

Asia WGS AF: 0.444 AC: 1546 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	-0.73
CADD	Benign	4.2
DANN	Benign	0.90

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7900024; hg19: chr10-27444763; COSMIC: COSV58761704; COSMIC: COSV58761704;