Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001172303.3(MASTL):c.1782C>T(p.Ile594Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.622 in 1,613,170 control chromosomes in the GnomAD database, including 315,882 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.60 ( 27755 hom., cov: 32)

Exomes 𝑓: 0.62 ( 288127 hom. )

Consequence

MASTL
NM_001172303.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.229

Publications

38 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):

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

ACBD5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 10-27170741-C-T is Benign according to our data. Variant chr10-27170741-C-T is described in ClinVar as Benign. ClinVar VariationId is 262115.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.229 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.644 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	HGVSp	Effect	Exon Rank	Protein
MASTL	NM_001172303.3	MANE Select	c.1782C>T	p.Ile594Ile	synonymous	Exon 8 of 12	NP_001165774.1
MASTL	NM_001320757.2		c.1782C>T	p.Ile594Ile	synonymous	Exon 8 of 13	NP_001307686.1
MASTL	NM_001320756.2		c.1782C>T	p.Ile594Ile	synonymous	Exon 8 of 13	NP_001307685.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MASTL	ENST00000375940.9	TSL:1 MANE Select	c.1782C>T	p.Ile594Ile	synonymous	Exon 8 of 12	ENSP00000365107.5
MASTL	ENST00000375946.8	TSL:1	c.1782C>T	p.Ile594Ile	synonymous	Exon 8 of 12	ENSP00000365113.4
MASTL	ENST00000342386.10	TSL:2	c.1782C>T	p.Ile594Ile	synonymous	Exon 8 of 11	ENSP00000343446.5

Frequencies

GnomAD3 genomes

AF:

0.601

AC:

91331

AN:

151866

Hom.:

27761

Cov.:

show subpopulations

Gnomad AFR

AF:

0.554

Gnomad AMI

AF:

0.622

Gnomad AMR

AF:

0.570

Gnomad ASJ

AF:

0.629

Gnomad EAS

AF:

0.427

Gnomad SAS

AF:

0.477

Gnomad FIN

AF:

0.662

Gnomad MID

AF:

0.585

Gnomad NFE

AF:

0.649

Gnomad OTH

AF:

0.595

GnomAD2 exomes

AF:

0.590

AC:

147703

AN:

250204

AF XY:

0.590

show subpopulations

Gnomad AFR exome

AF:

0.547

Gnomad AMR exome

AF:

0.536

Gnomad ASJ exome

AF:

0.617

Gnomad EAS exome

AF:

0.433

Gnomad FIN exome

AF:

0.663

Gnomad NFE exome

AF:

0.649

Gnomad OTH exome

AF:

0.616

GnomAD4 exome

AF:

0.624

AC:

912404

AN:

1461186

Hom.:

288127

Cov.:

AF XY:

0.621

AC XY:

451642

AN XY:

726908

show subpopulations

African (AFR)

AF:

0.554

AC:

18529

AN:

33470

American (AMR)

AF:

0.537

AC:

23998

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.619

AC:

16162

AN:

26124

East Asian (EAS)

AF:

0.398

AC:

15791

AN:

39680

South Asian (SAS)

AF:

0.491

AC:

42333

AN:

86208

European-Finnish (FIN)

AF:

0.661

AC:

35261

AN:

53338

Middle Eastern (MID)

AF:

0.578

AC:

3334

AN:

5766

European-Non Finnish (NFE)

AF:

0.648

AC:

720140

AN:

1111534

Other (OTH)

AF:

0.610

AC:

36856

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

19000

38000

57000

76000

95000

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18722

37444

56166

74888

93610

<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:

0.601

AC:

91335

AN:

151984

Hom.:

27755

Cov.:

AF XY:

0.600

AC XY:

44549

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.553

AC:

22905

AN:

41436

American (AMR)

AF:

0.570

AC:

8698

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.629

AC:

2181

AN:

3468

East Asian (EAS)

AF:

0.427

AC:

2201

AN:

5160

South Asian (SAS)

AF:

0.478

AC:

2308

AN:

4826

European-Finnish (FIN)

AF:

0.662

AC:

6990

AN:

10562

Middle Eastern (MID)

AF:

0.592

AC:

174

AN:

294

European-Non Finnish (NFE)

AF:

0.649

AC:

44075

AN:

67952

Other (OTH)

AF:

0.587

AC:

1236

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1860

3720

5579

7439

9299

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

764

1528

2292

3056

3820

<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:

0.629

Hom.:

75887

Bravo

AF:

0.593

Asia WGS

AF:

0.444

AC:

1546

AN:

3478

EpiCase

AF:

0.644

EpiControl

AF:

0.640

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Thrombocytopenia (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

3.5

(source)

DANN

Benign

0.62

PhyloP100

0.23

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs1981296

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over