rs36121140

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.1010C>A(p.Thr337Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00557 in 1,614,016 control chromosomes in the GnomAD database, including 302 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0057 ( 38 hom., cov: 33)

Exomes 𝑓: 0.0056 ( 264 hom. )

Consequence

MASTL
NM_001172303.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.108

Publications

9 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 (MetaRNN=0.0025212765).

BP6

Variant 10-27169969-C-A is Benign according to our data. Variant chr10-27169969-C-A is described in ClinVar as Benign. ClinVar VariationId is 262114.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.103 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	UniProt
MASTL	NM_001172303.3	MANE Select	c.1010C>A	p.Thr337Lys	missense	Exon 8 of 12	NP_001165774.1	Q96GX5-1
MASTL	NM_001320757.2		c.1010C>A	p.Thr337Lys	missense	Exon 8 of 13	NP_001307686.1
MASTL	NM_001320756.2		c.1010C>A	p.Thr337Lys	missense	Exon 8 of 13	NP_001307685.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MASTL	ENST00000375940.9	TSL:1 MANE Select	c.1010C>A	p.Thr337Lys	missense	Exon 8 of 12	ENSP00000365107.5	Q96GX5-1
MASTL	ENST00000375946.8	TSL:1	c.1010C>A	p.Thr337Lys	missense	Exon 8 of 12	ENSP00000365113.4	Q96GX5-3
MASTL	ENST00000969651.1		c.1010C>A	p.Thr337Lys	missense	Exon 8 of 13	ENSP00000639710.1

Frequencies

GnomAD3 genomes

AF:

0.00574

AC:

873

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000628

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.110

Gnomad SAS

AF:

0.0226

Gnomad FIN

AF:

0.00132

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00154

Gnomad OTH

AF:

0.00957

GnomAD2 exomes

AF:

0.0117

AC:

2940

AN:

250774

AF XY:

0.0119

show subpopulations

Gnomad AFR exome

AF:

0.000925

Gnomad AMR exome

AF:

0.00110

Gnomad ASJ exome

AF:

0.000497

Gnomad EAS exome

AF:

0.112

Gnomad FIN exome

AF:

0.00166

Gnomad NFE exome

AF:

0.00177

Gnomad OTH exome

AF:

0.00638

GnomAD4 exome

AF:

0.00555

AC:

8115

AN:

1461820

Hom.:

264

Cov.:

AF XY:

0.00598

AC XY:

4351

AN XY:

727208

show subpopulations

African (AFR)

AF:

0.00119

AC:

AN:

33480

American (AMR)

AF:

0.00114

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.000765

AC:

AN:

26134

East Asian (EAS)

AF:

0.100

AC:

3986

AN:

39688

South Asian (SAS)

AF:

0.0186

AC:

1605

AN:

86252

European-Finnish (FIN)

AF:

0.00225

AC:

120

AN:

53384

Middle Eastern (MID)

AF:

0.00277

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00154

AC:

1713

AN:

1111996

Other (OTH)

AF:

0.00934

AC:

564

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

424

848

1273

1697

2121

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

138

276

414

552

690

<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:

0.00574

AC:

873

AN:

152196

Hom.:

Cov.:

AF XY:

0.00660

AC XY:

491

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.000626

AC:

AN:

41516

American (AMR)

AF:

0.00177

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3472

East Asian (EAS)

AF:

0.110

AC:

570

AN:

5174

South Asian (SAS)

AF:

0.0224

AC:

108

AN:

4822

European-Finnish (FIN)

AF:

0.00132

AC:

AN:

10582

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00154

AC:

105

AN:

68028

Other (OTH)

AF:

0.00994

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

124

165

206

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00572

Hom.:

Bravo

AF:

0.00624

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00285

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00198

AC:

ExAC

AF:

0.0117

AC:

1416

Asia WGS

AF:

0.0420

AC:

146

AN:

3476

EpiCase

AF:

0.00169

EpiControl

AF:

0.00119

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (2)

not provided (1)

Thrombocytopenia (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.55

CADD

Benign

3.3

(source)

DANN

Benign

0.37

DEOGEN2

Benign

0.014

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.60

MetaRNN

Benign

0.0025

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

PhyloP100

-0.11

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.1

REVEL

Benign

0.033

Sift

Benign

0.060

Sift4G

Benign

0.88

Polyphen

0.0030

Vest4

0.034

MPC

0.13

ClinPred

0.0020

GERP RS

0.79

PromoterAI

-0.018

Neutral

(source)

Varity_R

0.034

gMVP

0.33

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

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