Genetic Variant MATK:p.Pro507Ser (chr19-3778188-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_139355.3(MATK):c.1519C>T(p.Pro507Ser) 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. 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

MATK
NM_139355.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.26

Publications

0 publications found

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]

MATK links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21850094).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139355.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MATK	NM_139355.3	MANE Select	c.1519C>T	p.Pro507Ser	missense	Exon 14 of 14	NP_647612.1	P42679-1
MATK	NM_002378.4		c.1522C>T	p.Pro508Ser	missense	Exon 14 of 14	NP_002369.2
MATK	NM_001440577.1		c.1519C>T	p.Pro507Ser	missense	Exon 14 of 14	NP_001427506.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MATK	ENST00000310132.11	TSL:1 MANE Select	c.1519C>T	p.Pro507Ser	missense	Exon 14 of 14	ENSP00000308734.5	P42679-1
MATK	ENST00000585778.5	TSL:1	c.1516C>T	p.Pro506Ser	missense	Exon 14 of 14	ENSP00000468030.1	K7EQY5
MATK	ENST00000395040.6	TSL:1	c.1396C>T	p.Pro466Ser	missense	Exon 13 of 13	ENSP00000378481.1	P42679-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1405386

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

697190

African (AFR)

AF:

0.00

AC:

AN:

31260

American (AMR)

AF:

0.00

AC:

AN:

31594

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24576

East Asian (EAS)

AF:

0.00

AC:

AN:

37618

South Asian (SAS)

AF:

0.00

AC:

AN:

80312

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46144

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5554

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1090114

Other (OTH)

AF:

0.00

AC:

AN:

58214

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Pathogenic

0.29

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

Eigen

Uncertain

0.22

Eigen_PC

Benign

0.13

FATHMM_MKL

Benign

0.71

LIST_S2

Uncertain

0.86

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.22

MetaSVM

Benign

-0.68

MutationAssessor

Benign

1.1

PhyloP100

1.3

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.89

REVEL

Benign

0.21

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.99

Vest4

0.20

MutPred

0.31

Gain of phosphorylation at P507 (P = 0.0025)

MVP

0.80

MPC

1.1

ClinPred

0.93

GERP RS

2.0

Varity_R

0.20

gMVP

0.36

Mutation Taster

=82/18

polymorphism

(source)

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over