Variant chr10-27170353-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001172303.3(MASTL):c.1394G>T(p.Cys465Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MASTL
NM_001172303.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.56

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23181668).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MASTL	NM_001172303.3 link	c.1394G>T	p.Cys465Phe	missense_variant	8/12	ENST00000375940.9	NP_001165774.1	Q96GX5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MASTL	ENST00000375940.9 link	c.1394G>T	p.Cys465Phe	missense_variant	8/12	1	NM_001172303.3	ENSP00000365107.5		Q96GX5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250264

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135554

show subpopulations

Gnomad AFR exome

AF:

0.0000630

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1461358

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726996

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 23, 2024

The c.1394G>T (p.C465F) alteration is located in exon 8 (coding exon 8) of the MASTL gene. This alteration results from a G to T substitution at nucleotide position 1394, causing the cysteine (C) at amino acid position 465 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.022

.;T;.;.

Eigen

Benign

0.019

Eigen_PC

Benign

-0.089

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.80

T;T;T;T

M_CAP

Benign

0.022

MetaRNN

Benign

0.23

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

M;M;M;.

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.7

N;N;N;.

REVEL

Benign

0.19

Sift

Benign

0.032

D;D;D;.

Sift4G

Uncertain

0.039

D;D;D;T

Polyphen

0.97

D;D;D;.

Vest4

0.25

MutPred

0.45

Loss of disorder (P = 0.0957);Loss of disorder (P = 0.0957);Loss of disorder (P = 0.0957);.;

MVP

0.39

MPC

0.42

ClinPred

0.20

GERP RS

3.9

Varity_R

0.13

gMVP

0.39

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over