rs73598041

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001172303.3(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
NM_001172303.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.14

Publications

7 publications found

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]

MASTL links:

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]

ACBD5 Gene-Disease associations (from GenCC):

acyl-CoA binding domain containing protein 5 deficiency
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
retinal dystrophy with leukodystrophy
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

ACBD5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001172303.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MASTL	NM_001172303.3	MANE Select	c.2483-33T>C	intron	N/A	NP_001165774.1	Q96GX5-1
MASTL	NM_001320757.2		c.2498-33T>C	intron	N/A	NP_001307686.1
MASTL	NM_001320756.2		c.2495-33T>C	intron	N/A	NP_001307685.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MASTL	ENST00000375940.9	TSL:1 MANE Select	c.2483-33T>C	intron	N/A	ENSP00000365107.5	Q96GX5-1
MASTL	ENST00000375946.8	TSL:1	c.2480-33T>C	intron	N/A	ENSP00000365113.4	Q96GX5-3
MASTL	ENST00000969651.1		c.2498-33T>C	intron	N/A	ENSP00000639710.1

Frequencies

GnomAD3 genomes

AF:

0.0558

AC:

8490

AN:

152180

Hom.:

255

Cov.:

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

GnomAD2 exomes

AF:

0.0439

AC:

11018

AN:

250982

AF XY:

0.0435

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 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.:

AF XY:

0.0467

AC XY:

33539

AN XY:

718024

show subpopulations

African (AFR)

AF:

0.0847

AC:

2796

AN:

33004

American (AMR)

AF:

0.0198

AC:

886

AN:

44690

Ashkenazi Jewish (ASJ)

AF:

0.0636

AC:

1655

AN:

26028

East Asian (EAS)

AF:

0.00195

AC:

AN:

39580

South Asian (SAS)

AF:

0.0350

AC:

3003

AN:

85820

European-Finnish (FIN)

AF:

0.0557

AC:

2975

AN:

53398

Middle Eastern (MID)

AF:

0.0405

AC:

232

AN:

5728

European-Non Finnish (NFE)

AF:

0.0487

AC:

53198

AN:

1092522

Other (OTH)

AF:

0.0477

AC:

2853

AN:

59760

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

3462

6923

10385

13846

17308

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1938

3876

5814

7752

9690

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0559

AC:

8511

AN:

152298

Hom.:

257

Cov.:

AF XY:

0.0547

AC XY:

4076

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.0825

AC:

3430

AN:

41552

American (AMR)

AF:

0.0330

AC:

505

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0674

AC:

234

AN:

3472

East Asian (EAS)

AF:

0.00308

AC:

AN:

5192

South Asian (SAS)

AF:

0.0321

AC:

155

AN:

4826

European-Finnish (FIN)

AF:

0.0519

AC:

551

AN:

10612

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0514

AC:

3497

AN:

68024

Other (OTH)

AF:

0.0435

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

411

822

1234

1645

2056

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

196

294

392

490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0580

Hom.:

Bravo

AF:

0.0561

Asia WGS

AF:

0.0350

AC:

123

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

6.3

(source)

DANN

Benign

0.46

PhyloP100

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over