rs7091723

chr10-27177236-C-A

Variant summary

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

The NM_001172303.3(MASTL):c.2267-3717C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.603 in 151,954 control chromosomes in the GnomAD database, including 27,972 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 0.60 (27972 hom., cov: 31)
• Consequence: MASTL NM_001172303.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.951

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=-0.96).
• 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.2267-3717C>A		intron_variant		ENST00000375940.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MASTL	ENST00000375940.9	c.2267-3717C>A		intron_variant		1	NM_001172303.3	P5

Frequencies

GnomAD3 genomes AF: 0.604 AC: 91682 AN: 151836 Hom.: 27976 Cov.: 31

Gnomad AFR AF: 0.563

Gnomad AMI AF: 0.620

Gnomad AMR AF: 0.571

Gnomad ASJ AF: 0.630

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.476

Gnomad FIN AF: 0.662

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.649

Gnomad OTH AF: 0.594

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

GnomAD4 genome AF: 0.603 AC: 91688 AN: 151954 Hom.: 27972 Cov.: 31 AF XY: 0.602 AC XY: 44725 AN XY: 74274

Gnomad4 AFR AF: 0.562

Gnomad4 AMR AF: 0.570

Gnomad4 ASJ AF: 0.630

Gnomad4 EAS AF: 0.425

Gnomad4 SAS AF: 0.477

Gnomad4 FIN AF: 0.662

Gnomad4 NFE AF: 0.649

Gnomad4 OTH AF: 0.587

Alfa AF: 0.631 Hom.: 3827

Bravo AF: 0.596

Asia WGS AF: 0.445 AC: 1550 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	3.5
Dann	Benign	0.20

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: rs7091723; hg19: chr10-27466165;