chr19-3778299-G-A

Position:

• chr19-3778299-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_139355.3(MATK):​c.1408C>T​(p.Pro470Ser) 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. 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: 33)
• Consequence: MATK NM_139355.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.784

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]

ACMG classification

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=0.07802391).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MATK	NM_139355.3	c.1408C>T	p.Pro470Ser	missense_variant	14/14	ENST00000310132.11	NP_647612.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MATK	ENST00000310132.11	c.1408C>T	p.Pro470Ser	missense_variant	14/14	1	NM_139355.3	ENSP00000308734.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 26, 2024

The c.1411C>T (p.P471S) alteration is located in exon 14 (coding exon 13) of the MATK gene. This alteration results from a C to T substitution at nucleotide position 1411, causing the proline (P) at amino acid position 471 to be replaced by a serine (S). 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	0.072
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	12
DANN	Benign	0.34
DEOGEN2	Benign	0.23	.;.;T;T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.74	T;T;T;T;.
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.078	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-1.0	.;.;N;.;.
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	1.3	.;N;N;.;N
REVEL	Benign	0.10
Sift	Benign	0.84	.;T;T;.;T
Sift4G	Benign	0.61	T;T;T;T;T
Polyphen		0.0030	.;.;B;.;.
Vest4		0.077
MutPred		0.37		.;.;Gain of phosphorylation at P470 (P = 0.0016);.;.;
MVP		0.48
MPC		0.53
ClinPred		0.045	T
GERP RS		2.6
Varity_R		0.024
gMVP		0.15

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-3778297;