rs138508775

Variant summary

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

The NM_139355.3(MATK):​c.635G>T​(p.Arg212Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,786 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

MATK
NM_139355.3 missense

Scores

2
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.72
Variant links:
Genes affected
MATK (HGNC:6906): (megakaryocyte-associated tyrosine kinase) The protein encoded by this gene has amino acid sequence similarity to Csk tyrosine kinase and has the structural features of the CSK subfamily: SRC homology SH2 and SH3 domains, a catalytic domain, a unique N terminus, lack of myristylation signals, lack of a negative regulatory phosphorylation site, and lack of an autophosphorylation site. This protein is thought to play a significant role in the signal transduction of hematopoietic cells. It is able to phosphorylate and inactivate Src family kinases, and may play an inhibitory role in the control of T-cell proliferation. This protein might be involved in signaling in some cases of breast cancer. Three alternatively spliced transcript variants that encode different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

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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=0.20300141).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MATKNM_139355.3 linkc.635G>T p.Arg212Leu missense_variant Exon 7 of 14 ENST00000310132.11 NP_647612.1 P42679-1F1T0G6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MATKENST00000310132.11 linkc.635G>T p.Arg212Leu missense_variant Exon 7 of 14 1 NM_139355.3 ENSP00000308734.5 P42679-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461786
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
727214
show subpopulations
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.070
T
BayesDel_noAF
Benign
-0.34
CADD
Benign
21
DANN
Benign
0.95
DEOGEN2
Benign
0.15
.;.;T;T;.;T;T;T
Eigen
Benign
-0.31
Eigen_PC
Benign
-0.22
FATHMM_MKL
Uncertain
0.85
D
LIST_S2
Uncertain
0.86
D;D;D;D;.;D;D;D
M_CAP
Benign
0.048
D
MetaRNN
Benign
0.20
T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.55
.;.;N;.;.;.;.;.
PrimateAI
Benign
0.44
T
PROVEAN
Benign
-0.92
.;N;N;.;N;.;.;.
REVEL
Benign
0.039
Sift
Benign
0.35
.;T;T;.;T;.;.;.
Sift4G
Benign
0.32
T;T;T;T;T;T;T;.
Polyphen
0.39
.;.;B;.;.;.;.;.
Vest4
0.23
MutPred
0.39
.;.;Loss of methylation at K211 (P = 0.032);Loss of methylation at K211 (P = 0.032);.;.;.;.;
MVP
0.85
MPC
0.66
ClinPred
0.31
T
GERP RS
3.6
Varity_R
0.41
gMVP
0.63

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-3783165; API