rs788219

Positions:

• chr10-27184306-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001172303.3(MASTL):​c.2483-2073G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0883 in 152,226 control chromosomes in the GnomAD database, including 813 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.088 (813 hom., cov: 32)
• Consequence: MASTL NM_001172303.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.56

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]

ACBD5 (HGNC:23338): (acyl-CoA binding domain containing 5) This gene encodes a member of the acyl-Coenzyme A binding protein family, known to function in the transport and distribution of long chain acyl-Coenzyme A in cells. This gene may play a role in the differentiation of megakaryocytes and formation of platelets. A related protein in yeast is involved in autophagy of peroxisomes. A mutation in this gene has been associated with autosomal dominant thrombocytopenia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MASTL	NM_001172303.3	c.2483-2073G>A		intron_variant		ENST00000375940.9	NP_001165774.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MASTL	ENST00000375940.9	c.2483-2073G>A		intron_variant		1	NM_001172303.3	ENSP00000365107	P5

Frequencies

GnomAD3 genomes AF: 0.0884 AC: 13452 AN: 152108 Hom.: 813 Cov.: 32

Gnomad AFR AF: 0.0255

Gnomad AMI AF: 0.172

Gnomad AMR AF: 0.0954

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0762

Gnomad FIN AF: 0.0539

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.111

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

GnomAD4 genome AF: 0.0883 AC: 13445 AN: 152226 Hom.: 813 Cov.: 32 AF XY: 0.0823 AC XY: 6123 AN XY: 74438

Gnomad4 AFR AF: 0.0254

Gnomad4 AMR AF: 0.0953

Gnomad4 ASJ AF: 0.116

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0765

Gnomad4 FIN AF: 0.0539

Gnomad4 NFE AF: 0.135

Gnomad4 OTH AF: 0.110

Alfa AF: 0.124 Hom.: 671

Bravo AF: 0.0881

Asia WGS AF: 0.0320 AC: 112 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	4.2
DANN	Benign	0.84

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: rs788219; hg19: chr10-27473235;