rs541647241

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_139355.3(MATK):​c.1195G>T​(p.Gly399Trp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000713 in 1,403,300 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

MATK
NM_139355.3 missense, splice_region

Scores

3
13
3
Splicing: ADA: 0.1141
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.33
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.792

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MATKNM_139355.3 linkc.1195G>T p.Gly399Trp missense_variant, splice_region_variant Exon 12 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.1195G>T p.Gly399Trp missense_variant, splice_region_variant Exon 12 of 14 1 NM_139355.3 ENSP00000308734.5 P42679-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
7.13e-7
AC:
1
AN:
1403300
Hom.:
0
Cov.:
32
AF XY:
0.00000144
AC XY:
1
AN XY:
693910
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000256
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.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.54
BayesDel_addAF
Uncertain
0.027
T
BayesDel_noAF
Benign
-0.20
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.86
.;.;D;D;.
Eigen
Uncertain
0.53
Eigen_PC
Uncertain
0.40
FATHMM_MKL
Benign
0.62
D
LIST_S2
Uncertain
0.92
D;D;D;D;.
M_CAP
Pathogenic
0.49
D
MetaRNN
Pathogenic
0.76
D;D;D;D;D
MetaSVM
Uncertain
-0.071
T
MutationAssessor
Uncertain
2.7
.;.;M;.;.
PrimateAI
Uncertain
0.62
T
PROVEAN
Uncertain
-4.1
.;D;D;.;D
REVEL
Uncertain
0.41
Sift
Uncertain
0.0070
.;D;D;.;D
Sift4G
Uncertain
0.0050
D;D;D;D;D
Polyphen
1.0
.;.;D;.;.
Vest4
0.47
MutPred
0.68
.;.;Loss of disorder (P = 0.0129);Loss of disorder (P = 0.0129);.;
MVP
0.90
MPC
1.6
ClinPred
0.98
D
GERP RS
3.1
Varity_R
0.45
gMVP
0.61

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.11
dbscSNV1_RF
Benign
0.55
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-3778992; COSMIC: COSV100035821; COSMIC: COSV100035821; API