rs788237

chr10-27169003-C-T

Variant summary

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

The NM_001172303.3(MASTL):c.985-941C>T 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 151,874 control chromosomes in the GnomAD database, including 1,881 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 0.14 (1881 hom., cov: 31)
• Consequence: MASTL NM_001172303.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.792

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=-0.92).
• 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.985-941C>T		intron_variant		ENST00000375940.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MASTL	ENST00000375940.9	c.985-941C>T		intron_variant		1	NM_001172303.3	P5
MASTL	ENST00000375946.8	c.985-941C>T		intron_variant		1		A1
ACBD5	ENST00000677440.1	c.*1228G>A		3_prime_UTR_variant	13/13
MASTL	ENST00000342386.10	c.985-941C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21835 AN: 151756 Hom.: 1873 Cov.: 31

Gnomad AFR AF: 0.0995

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.0102

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.0680

Gnomad MID AF: 0.218

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: 21863 AN: 151874 Hom.: 1881 Cov.: 31 AF XY: 0.136 AC XY: 10089 AN XY: 74206

Gnomad4 AFR AF: 0.0996

Gnomad4 AMR AF: 0.225

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.0103

Gnomad4 SAS AF: 0.112

Gnomad4 FIN AF: 0.0680

Gnomad4 NFE AF: 0.175

Gnomad4 OTH AF: 0.171

Alfa AF: 0.156 Hom.: 265

Bravo AF: 0.156

Asia WGS AF: 0.0670 AC: 235 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.52
Dann	Benign	0.21

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: rs788237; hg19: chr10-27457932;