rs73598041

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000375940.9(MASTL):​c.2483-33T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0478 in 1,592,828 control chromosomes in the GnomAD database, including 2,009 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.056 ( 257 hom., cov: 33)
Exomes 𝑓: 0.047 ( 1752 hom. )

Consequence

MASTL
ENST00000375940.9 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.14
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
Variant 10-27186346-T-C is Benign according to our data. Variant chr10-27186346-T-C is described in ClinVar as [Benign]. Clinvar id is 262121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0802 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MASTLNM_001172303.3 linkuse as main transcriptc.2483-33T>C intron_variant ENST00000375940.9 NP_001165774.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MASTLENST00000375940.9 linkuse as main transcriptc.2483-33T>C intron_variant 1 NM_001172303.3 ENSP00000365107 P5Q96GX5-1

Frequencies

GnomAD3 genomes
AF:
0.0558
AC:
8490
AN:
152180
Hom.:
255
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0822
Gnomad AMI
AF:
0.0219
Gnomad AMR
AF:
0.0330
Gnomad ASJ
AF:
0.0674
Gnomad EAS
AF:
0.00307
Gnomad SAS
AF:
0.0323
Gnomad FIN
AF:
0.0519
Gnomad MID
AF:
0.0443
Gnomad NFE
AF:
0.0514
Gnomad OTH
AF:
0.0440
GnomAD3 exomes
AF:
0.0439
AC:
11018
AN:
250982
Hom.:
310
AF XY:
0.0435
AC XY:
5906
AN XY:
135736
show subpopulations
Gnomad AFR exome
AF:
0.0832
Gnomad AMR exome
AF:
0.0188
Gnomad ASJ exome
AF:
0.0631
Gnomad EAS exome
AF:
0.00348
Gnomad SAS exome
AF:
0.0346
Gnomad FIN exome
AF:
0.0553
Gnomad NFE exome
AF:
0.0512
Gnomad OTH exome
AF:
0.0415
GnomAD4 exome
AF:
0.0470
AC:
67675
AN:
1440530
Hom.:
1752
Cov.:
28
AF XY:
0.0467
AC XY:
33539
AN XY:
718024
show subpopulations
Gnomad4 AFR exome
AF:
0.0847
Gnomad4 AMR exome
AF:
0.0198
Gnomad4 ASJ exome
AF:
0.0636
Gnomad4 EAS exome
AF:
0.00195
Gnomad4 SAS exome
AF:
0.0350
Gnomad4 FIN exome
AF:
0.0557
Gnomad4 NFE exome
AF:
0.0487
Gnomad4 OTH exome
AF:
0.0477
GnomAD4 genome
AF:
0.0559
AC:
8511
AN:
152298
Hom.:
257
Cov.:
33
AF XY:
0.0547
AC XY:
4076
AN XY:
74474
show subpopulations
Gnomad4 AFR
AF:
0.0825
Gnomad4 AMR
AF:
0.0330
Gnomad4 ASJ
AF:
0.0674
Gnomad4 EAS
AF:
0.00308
Gnomad4 SAS
AF:
0.0321
Gnomad4 FIN
AF:
0.0519
Gnomad4 NFE
AF:
0.0514
Gnomad4 OTH
AF:
0.0435
Alfa
AF:
0.0576
Hom.:
54
Bravo
AF:
0.0561
Asia WGS
AF:
0.0350
AC:
123
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxJun 19, 2021- -
not specified Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
CADD
Benign
6.3
DANN
Benign
0.46

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs73598041; hg19: chr10-27475275; API