NM_001172303.3:c.2139G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001172303.3(MASTL):c.2139G>A(p.Gln713Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0167 in 1,614,040 control chromosomes in the GnomAD database, including 331 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 22 hom., cov: 31)

Exomes 𝑓: 0.017 ( 309 hom. )

Consequence

MASTL
NM_001172303.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0870

Publications

3 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=-0.67).

BP6

Variant 10-27173132-G-A is Benign according to our data. Variant chr10-27173132-G-A is described in ClinVar as Benign. ClinVar VariationId is 262119.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.087 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0119 (1817/152242) while in subpopulation SAS AF = 0.0336 (162/4820). AF 95% confidence interval is 0.0294. There are 22 homozygotes in GnomAd4. There are 884 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High AC in GnomAd4 at 1817 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MASTL	NM_001172303.3 link	c.2139G>A	p.Gln713Gln	synonymous_variant	Exon 9 of 12	ENST00000375940.9	NP_001165774.1	Q96GX5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MASTL	ENST00000375940.9 link	c.2139G>A	p.Gln713Gln	synonymous_variant	Exon 9 of 12	1	NM_001172303.3	ENSP00000365107.5		Q96GX5-1

Frequencies

GnomAD3 genomes

AF:

0.0120

AC:

1818

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00268

Gnomad AMI

AF:

0.104

Gnomad AMR

AF:

0.00373

Gnomad ASJ

AF:

0.0156

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0336

Gnomad FIN

AF:

0.0232

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0156

Gnomad OTH

AF:

0.0110

GnomAD2 exomes

AF:

0.0159

AC:

3989

AN:

251404

AF XY:

0.0178

show subpopulations

Gnomad AFR exome

AF:

0.00295

Gnomad AMR exome

AF:

0.00376

Gnomad ASJ exome

AF:

0.0178

Gnomad EAS exome

AF:

0.000217

Gnomad FIN exome

AF:

0.0238

Gnomad NFE exome

AF:

0.0160

Gnomad OTH exome

AF:

0.0173

GnomAD4 exome

AF:

0.0171

AC:

25069

AN:

1461798

Hom.:

309

Cov.:

AF XY:

0.0181

AC XY:

13132

AN XY:

727214

show subpopulations

African (AFR)

AF:

0.00257

AC:

AN:

33478

American (AMR)

AF:

0.00425

AC:

190

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0166

AC:

434

AN:

26136

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39696

South Asian (SAS)

AF:

0.0383

AC:

3303

AN:

86250

European-Finnish (FIN)

AF:

0.0272

AC:

1454

AN:

53418

Middle Eastern (MID)

AF:

0.0324

AC:

187

AN:

5768

European-Non Finnish (NFE)

AF:

0.0166

AC:

18465

AN:

1111932

Other (OTH)

AF:

0.0157

AC:

947

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

1248

2496

3743

4991

6239

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

712

1424

2136

2848

3560

<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:

0.0119

AC:

1817

AN:

152242

Hom.:

Cov.:

AF XY:

0.0119

AC XY:

884

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.00267

AC:

111

AN:

41556

American (AMR)

AF:

0.00373

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0156

AC:

AN:

3470

East Asian (EAS)

AF:

0.000386

AC:

AN:

5180

South Asian (SAS)

AF:

0.0336

AC:

162

AN:

4820

European-Finnish (FIN)

AF:

0.0232

AC:

246

AN:

10600

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0156

AC:

1063

AN:

68012

Other (OTH)

AF:

0.0109

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

177

266

354

443

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<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:

0.0144

Hom.:

Bravo

AF:

0.00976

Asia WGS

AF:

0.0130

AC:

AN:

3478

EpiCase

AF:

0.0156

EpiControl

AF:

0.0159

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Thrombocytopenia

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.48

(source)

DANN

Benign

0.63

PhyloP100

0.087

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over