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GeneBe

10-27170365-A-G

Variant summary

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

The NM_001172303.3(MASTL):c.1406A>G(p.Lys469Arg) 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

MASTL
NM_001172303.3 missense

Scores

18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.62
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]
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]

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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=0.08076033).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MASTLNM_001172303.3 linkuse as main transcriptc.1406A>G p.Lys469Arg missense_variant 8/12 ENST00000375940.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MASTLENST00000375940.9 linkuse as main transcriptc.1406A>G p.Lys469Arg missense_variant 8/121 NM_001172303.3 P5Q96GX5-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.0000113

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 submitterclinical testingAmbry GeneticsFeb 14, 2023The c.1406A>G (p.K469R) alteration is located in exon 8 (coding exon 8) of the MASTL gene. This alteration results from a A to G substitution at nucleotide position 1406, causing the lysine (K) at amino acid position 469 to be replaced by an arginine (R). 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
0.070
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.56
Cadd
Benign
7.2
Dann
Benign
0.94
Eigen
Benign
-0.94
Eigen_PC
Benign
-0.97
FATHMM_MKL
Benign
0.21
N
LIST_S2
Benign
0.65
T;T;T;T
M_CAP
Benign
0.018
T
MetaRNN
Benign
0.081
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.1
L;L;L;.
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.27
T
PROVEAN
Benign
-0.30
N;N;N;.
REVEL
Benign
0.11
Sift
Benign
0.092
T;T;T;.
Sift4G
Benign
0.39
T;T;T;T
Polyphen
0.0040
B;B;B;.
Vest4
0.076
MutPred
0.48
Loss of ubiquitination at K469 (P = 0.0059);Loss of ubiquitination at K469 (P = 0.0059);Loss of ubiquitination at K469 (P = 0.0059);.;
MVP
0.22
MPC
0.090
ClinPred
0.080
T
GERP RS
-1.6
Varity_R
0.024
gMVP
0.25

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.

Other links and lift over

dbSNP: rs2057888770; hg19: chr10-27459294; API